|
1
|
Crocetto F, Calogero A, Santangelo M, Fernicola A, Varlese F, Mirto BF, Machiella F, Falcone A, Pagano G, Dinacci F, Giampaglia G, Varriale D, Trama F, Iaconis S, Del Giudice F, Busetto GM, Ferro M, Lasorsa F, Lucarelli G, Imbimbo C, Barone B. The Role of Butirprost ® as an Adjuvant in Enhancing the Effect of Antibiotics in Patients Affected by Chronic Bacterial Prostatitis: A Randomized Prospective Trial. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:148. [PMID: 39859130 PMCID: PMC11767095 DOI: 10.3390/medicina61010148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/22/2024] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
Bacterial prostatitis (BP) is a common prostatic infection characterized by pain and urinary symptoms, often with negative bacterial cultures from prostatic secretions. It affects young and older men bimodally and impacts quality of life (QoL) significantly. Background and Objectives: Treatment typically involves antibiotics, but a multimodal approach with additional nutraceuticals may enhance outcomes. This study aimed to assess the efficacy of Butirprost® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP). Materials and Methods: Patients diagnosed with prostatitis (positive Meares-Stamey test and symptom duration > 3 months) at the University of Naples "Federico II", Italy, from March 2024 to July 2024 were included in this study. All patients underwent bacterial cultures. Patients were randomized into two groups: Group A received antibiotics plus Butirprost® (sodium hyaluronate plus Plantago major) for one month, while Group B received antibiotics alone. International Prostatic Symptoms Score (IPSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaires were administered at baseline and at 15 and 30 days. Results: Out of 60 patients (Group A: 30, Group B: 30), Group A showed significant improvement in IPSS and NIH-CPSI scores at 15 and 30 days compared to Group B. Notable improvements were observed in pain, urinary symptoms, and QoL. Conclusions: The administration of Butirprost® along with fluoroquinolones resulted in a significant improvement in pain, urinary symptoms, and quality of life along with improvements in both IPSS and NIH-CPSI scores, in patients affected by chronic bacterial prostatitis compared with fluoroquinolones alone.
Collapse
Affiliation(s)
- Felice Crocetto
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Armando Calogero
- Section of General Surgery, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy; (A.C.); (M.S.); (A.F.); (F.V.)
| | - Michele Santangelo
- Section of General Surgery, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy; (A.C.); (M.S.); (A.F.); (F.V.)
| | - Agostino Fernicola
- Section of General Surgery, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy; (A.C.); (M.S.); (A.F.); (F.V.)
| | - Filippo Varlese
- Section of General Surgery, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy; (A.C.); (M.S.); (A.F.); (F.V.)
| | - Benito Fabio Mirto
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Fabio Machiella
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Alfonso Falcone
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Giovanni Pagano
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Fabrizio Dinacci
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Gaetano Giampaglia
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Domenico Varriale
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Francesco Trama
- Urology Complex Unit, ASL Napoli 2 Nord ‘Santa Maria delle Grazie’ Hospital, 80078 Pozzuoli, Italy;
| | - Salvatore Iaconis
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Francesco Del Giudice
- Department of Urology, Policlinico Umberto I, Sapienza University of Rome, 00185 Rome, Italy;
| | - Gian Maria Busetto
- Department of Urology and Organ Transplantation, University of Foggia, 71122 Foggia, Italy; (G.M.B.); (F.L.)
| | - Matteo Ferro
- Division of Urology, European Institute of Oncology (IEO) IRCCS, 20139 Milan, Italy;
| | - Francesco Lasorsa
- Department of Urology and Organ Transplantation, University of Foggia, 71122 Foggia, Italy; (G.M.B.); (F.L.)
| | - Giuseppe Lucarelli
- Urology, Andrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area-Urology, University of Bari “Aldo Moro”, 70121 Bari, Italy;
| | - Ciro Imbimbo
- Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (F.C.); (B.F.M.); (F.M.); (A.F.); (G.P.); (F.D.); (G.G.); (D.V.); (S.I.); (C.I.)
| | - Biagio Barone
- Department of Urology, 196152 Ospedale San Paolo, ASL NA1 Centro Naples, 80145 Naples, Italy
| |
Collapse
|
|
2
|
Gilbertie JM, Sheahan BJ, Vaden SL, Jacob ME. Canine urothelial cell model to study intracellular bacterial community development by uropathogenic Escherichia coli. PLoS One 2025; 20:e0316834. [PMID: 39787183 PMCID: PMC11717241 DOI: 10.1371/journal.pone.0316834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 12/17/2024] [Indexed: 01/12/2025] Open
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections of both dogs and humans, with most caused by uropathogenic Escherichia coli (UPEC). Recurrent UPEC infections are a major concern in the treatment and management of UTIs in both species. In humans, the ability of UPECs to form intracellular bacterial communities (IBCs) within urothelial cells has been implicated in recurrent UTIs. However, the role of IBCs has not been explored in the pathogenesis of canine recurrent UTIs. In this study, we identified IBCs in both urine and bladder tissue from dogs with UPEC associated UTIs. In addition, we showed that UPECs derived from canine UTIs form IBCs within primary canine urothelial cells. As in human UTIs, formation of IBCs by canine UPECs correlated with the presence of the fimH gene as those isolates lacking the fimH gene formed fewer IBCs in canine urothelial cells then those harboring the fimH gene. Additionally, UPEC strains from clinical cases classified as recurrent UTIs had higher rates of IBC formation than UPEC strains from non-recurrent UTIs. These IBCs were tolerant to treatment with enrofloxacin, cefpodoxime and doxycycline at 150, 50 and 50 μg/mL respectively, which are representative of the concentrations achieved in canine urine after standard dosing. This is consistent with the clinical perspective that current UTIs are a common condition of dogs and are difficult to manage through antimicrobial treatment. Additionally, the dog could prove to be a powerful model of IBC formation as they are natural models of UPEC-causing UTIs and have similar pathophysiology of IBC formation.
Collapse
Affiliation(s)
- Jessica M. Gilbertie
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America
| | - Breanna J. Sheahan
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina United States of America
| | - Shelly L. Vaden
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina United States of America
| | - Megan E. Jacob
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America
| |
Collapse
|
|
3
|
Sharma A, Kumar Y, Kumar G, Tahlan AK. Biofilm Production and Antibiogram Profiles in Escherichia coli and Salmonella. Indian J Microbiol 2024; 64:1512-1517. [PMID: 39678983 PMCID: PMC11645373 DOI: 10.1007/s12088-023-01149-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 11/14/2023] [Indexed: 12/17/2024] Open
Abstract
Salmonella and Escherichia coli are important enteric pathogens associated with a variety of infections. Biofilm formation and antimicrobial resistance are important characteristics making these pathogens a concern in terms of strong attachment to substrates, expression of virulence markers and difficult removal. The present study investigates the biofilm-forming ability and antibiogram patterns among E. coli and Salmonella spp. A total of 200 E. coli and 100 Salmonella isolates received at National Salmonella and Escherichia Centre were identified by biochemical testing, followed by serotyping. Biofilm production was detected by Tissue Culture Plate method. The isolates were further subjected to Antibiotic Susceptibility Testing by the Kirby-Bauer disk diffusion method. 113 (56.5%) E. coli isolates and 79 (79%) Salmonella isolates were detected as biofilm producers. A total of 114(57%)E. coli isolates and 31(31%) Salmonella isolates were found to be resistant to multiple drugs when Antibiotic Susceptibility Testing was carried out. Antibiotic resistance was found to be significantly higher in biofilm producing salmonella (p = 0.001) whereas in the case of E. coli the difference remained non-significant (p = 0.4454). The capability to produce biofilm along with acquiring high level of antimicrobial resistance in salmonella and E. coli provide enhanced survival potential in adverse environments. Therefore, it becomes a serious cause of concern for public health authorities considering the virulence of these bacteria and their association with different disease conditions and requires urgent intervention with regards to control and prevention strategies.
Collapse
Affiliation(s)
- A. Sharma
- National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, Himachal Pradesh 173204 India
| | - Y. Kumar
- National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, Himachal Pradesh 173204 India
| | - G. Kumar
- National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, Himachal Pradesh 173204 India
| | - A. K. Tahlan
- National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, Himachal Pradesh 173204 India
| |
Collapse
|
|
4
|
Bhavnani SM, Hammel JP, Rubino CM, Talley AK, Eckburg PB, Liolios K, Gupta VK, Ambrose PG, Hamed KA, Melnick DA. Evaluation of Factors Predictive of Efficacy Among Patients With Complicated Urinary Tract Infection and/or Acute Pyelonephritis. Open Forum Infect Dis 2024; 11:ofae375. [PMID: 39229288 PMCID: PMC11370788 DOI: 10.1093/ofid/ofae375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 07/12/2024] [Indexed: 09/05/2024] Open
Abstract
Background Antibiotic treatment for complicated urinary tract infections (cUTI)/acute pyelonephritis (AP) is often followed by recurrent bacteriuria in the absence of clinical symptoms. To understand factors predictive of clinical and microbiologic outcomes in patients with cUTI/AP, multivariable analyses were undertaken using pooled data from a global, phase 3 cUTI study. Methods Using data from 366 tebipenem pivoxil hydrobromide- and 378 ertapenem-treated patients from the Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) infected with Enterobacterales uropathogens, multivariable analyses for dichotomous efficacy endpoints were performed using logistic regression and pharmacokinetic-pharmacodynamic relationships were evaluated. Results Urinary tract anatomical disorders and functional urinary tract or metabolic disorders were predictive of nonresponse across all efficacy endpoints assessed at test-of-cure (TOC) and late follow-up (LFU) visits, with greater impact on overall and microbiologic than clinical nonresponse. Independent variables predictive of increased probabilities of successful overall response at TOC and microbiologic response at TOC or LFU were baseline creatinine clearance >50 mL/min and baseline pathogen fluoroquinolone susceptibility. Infection with a phenotypic extended-spectrum beta-lactamase-positive Enterobacterales pathogen was predictive of reduced probabilities of success for microbiologic response at LFU and clinical response at TOC. Meaningful relationships between efficacy endpoints and plasma pharmacokinetic-pharmacodynamic indices were not identified. Conclusions Reductions of overall and microbiologic response in patients with cUTI/AP were associated with anatomical or functional urinary tract disorders, but not with the magnitude or duration of plasma antibiotic exposure. Results of these analyses serve to advance our understanding of factors predictive of outcome in patients with cUTI/AP.
Collapse
Affiliation(s)
- Sujata M Bhavnani
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| | - Jeffrey P Hammel
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| | | | | | | | - Kathryn Liolios
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| | - Vipul K Gupta
- Spero Therapeutics, Inc., Cambridge, Massachusetts, USA
| | - Paul G Ambrose
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| | - Kamal A Hamed
- Spero Therapeutics, Inc., Cambridge, Massachusetts, USA
| | | |
Collapse
|
|
5
|
Asgharzadeh Kangachar S, Logel DY, Trofimova E, Zhu HX, Zaugg J, Schembri MA, Weynberg KD, Jaschke PR. Discovery and characterisation of new phage targeting uropathogenic Escherichia coli. Virology 2024; 597:110148. [PMID: 38941748 DOI: 10.1016/j.virol.2024.110148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/02/2024] [Accepted: 06/18/2024] [Indexed: 06/30/2024]
Abstract
Antimicrobial resistance is an escalating threat with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of the most prevalent bacterial infections globally and are prone to becoming recurrent and antibiotic resistant. We discovered and characterized six novel Autographiviridae and Guernseyvirinae bacterial viruses (phage) against uropathogenic Escherichia coli (UPEC), a leading cause of UTIs. The phage genomes were between 39,471 bp - 45,233 bp, with 45.0%-51.0% GC%, and 57-84 predicted coding sequences per genome. We show that tail fiber domain structure, predicted host capsule type, and host antiphage repertoire correlate with phage host range. In vitro characterisation of phage cocktails showed synergistic improvement against a mixed UPEC strain population and when sequentially dosed. Together, these phage are a new set extending available treatments for UTI from UPEC, and phage vM_EcoM_SHAK9454 represents a promising candidate for further improvement through engineering.
Collapse
Affiliation(s)
- Shahla Asgharzadeh Kangachar
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
| | - Dominic Y Logel
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia
| | - Ellina Trofimova
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia
| | - Hannah X Zhu
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia
| | - Julian Zaugg
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
| | - Mark A Schembri
- Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, Queensland, Australia; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
| | - Karen D Weynberg
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
| | - Paul R Jaschke
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
| |
Collapse
|
|
6
|
Li M, Cruz CD, Ilina P, Tammela P. High-throughput combination assay for studying biofilm formation of uropathogenic Escherichia coli. Arch Microbiol 2024; 206:344. [PMID: 38967798 PMCID: PMC11226472 DOI: 10.1007/s00203-024-04029-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 05/23/2024] [Accepted: 06/03/2024] [Indexed: 07/06/2024]
Abstract
Uropathogenic Escherichia coli, the most common cause for urinary tract infections, forms biofilm enhancing its antibiotic resistance. To assess the effects of compounds on biofilm formation of uropathogenic Escherichia coli UMN026 strain, a high-throughput combination assay using resazurin followed by crystal violet staining was optimized for 384-well microplate. Optimized assay parameters included, for example, resazurin and crystal violet concentrations, and incubation time for readouts. For the assay validation, quality parameters Z' factor, coefficient of variation, signal-to-noise, and signal-to-background were calculated. Microplate uniformity, signal variability, edge well effects, and fold shift were also assessed. Finally, a screening with known antibacterial compounds was conducted to evaluate the assay performance. The best conditions found were achieved by using 12 µg/mL resazurin for 150 min and 0.023% crystal violet. This assay was able to detect compounds displaying antibiofilm activity against UMN026 strain at sub-inhibitory concentrations, in terms of metabolic activity and/or biomass.
Collapse
Affiliation(s)
- M Li
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland
| | - C D Cruz
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland
| | - P Ilina
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland
| | - P Tammela
- Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
| |
Collapse
|
|
7
|
Priyadarshini E, Kumar R, Balakrishnan K, Pandit S, Kumar R, Jha NK, Gupta PK. Biofilm Inhibition on Medical Devices and Implants Using Carbon Dots: An Updated Review. ACS APPLIED BIO MATERIALS 2024; 7:2604-2619. [PMID: 38622845 DOI: 10.1021/acsabm.4c00024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
Biofilms are an intricate community of microbes that colonize solid surfaces, communicating via a quorum-sensing mechanism. These microbial aggregates secrete exopolysaccharides facilitating adhesion and conferring resistance to drugs and antimicrobial agents. The escalating global concern over biofilm-related infections on medical devices underscores the severe threat to human health. Carbon dots (CDs) have emerged as a promising substrate to combat microbes and disrupt biofilm matrices. Their numerous advantages such as facile surface functionalization and specific antimicrobial properties, position them as innovative anti-biofilm agents. Due to their minuscule size, CDs can penetrate microbial cells, inhibiting growth via cytoplasmic leakage, reactive oxygen species (ROS) generation, and genetic material fragmentation. Research has demonstrated the efficacy of CDs in inhibiting biofilms formed by key pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Consequently, the development of CD-based coatings and hydrogels holds promise for eradicating biofilm formation, thereby enhancing treatment efficacy, reducing clinical expenses, and minimizing the need for implant revision surgeries. This review provides insights into the mechanisms of biofilm formation on implants, surveys major biofilm-forming pathogens and associated infections, and specifically highlights the anti-biofilm properties of CDs emphasizing their potential as coatings on medical implants.
Collapse
Affiliation(s)
- Eepsita Priyadarshini
- School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India
| | - Rohit Kumar
- Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, 201310 Uttar Pradesh, India
| | - Kalpana Balakrishnan
- Department of Biotechnology, K.S. Rangasamy College of Technology, Tiruchengode, Namakkal, 637215 Tamil Nadu, India
| | - Soumya Pandit
- Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, 201310 Uttar Pradesh, India
| | - Ranvijay Kumar
- Department of Mechanical Engineering, University Centre for Research and Development, Chandigarh University, Mohali, 140413 Punjab, India
| | - Niraj Kumar Jha
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 602105 Tamil Nadu, India
- Centre of Research Impact and Outcome, Chitkara University, Rajpura, 140401 Punjab, India
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411 Punjab, India
| | - Piyush Kumar Gupta
- Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, 201310 Uttar Pradesh, India
- Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, 248002 Uttarakhand, India
| |
Collapse
|
|
8
|
Bouhrour N, Nibbering PH, Bendali F. Medical Device-Associated Biofilm Infections and Multidrug-Resistant Pathogens. Pathogens 2024; 13:393. [PMID: 38787246 PMCID: PMC11124157 DOI: 10.3390/pathogens13050393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/29/2024] [Accepted: 05/04/2024] [Indexed: 05/25/2024] Open
Abstract
Medical devices such as venous catheters (VCs) and urinary catheters (UCs) are widely used in the hospital setting. However, the implantation of these devices is often accompanied by complications. About 60 to 70% of nosocomial infections (NIs) are linked to biofilms. The main complication is the ability of microorganisms to adhere to surfaces and form biofilms which protect them and help them to persist in the host. Indeed, by crossing the skin barrier, the insertion of VC inevitably allows skin flora or accidental environmental contaminants to access the underlying tissues and cause fatal complications like bloodstream infections (BSIs). In fact, 80,000 central venous catheters-BSIs (CVC-BSIs)-mainly occur in intensive care units (ICUs) with a death rate of 12 to 25%. Similarly, catheter-associated urinary tract infections (CA-UTIs) are the most commonlyhospital-acquired infections (HAIs) worldwide.These infections represent up to 40% of NIs.In this review, we present a summary of biofilm formation steps. We provide an overview of two main and important infections in clinical settings linked to medical devices, namely the catheter-asociated bloodstream infections (CA-BSIs) and catheter-associated urinary tract infections (CA-UTIs), and highlight also the most multidrug resistant bacteria implicated in these infections. Furthermore, we draw attention toseveral useful prevention strategies, and advanced antimicrobial and antifouling approaches developed to reduce bacterial colonization on catheter surfaces and the incidence of the catheter-related infections.
Collapse
Affiliation(s)
- Nesrine Bouhrour
- Laboratoire de Microbiologie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria;
| | - Peter H. Nibbering
- Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
| | - Farida Bendali
- Laboratoire de Microbiologie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria;
| |
Collapse
|
|
9
|
Al-Rabia MW, Asfour HZ, Alhakamy NA, Abdulaal WH, Ibrahim TS, Abbas HA, Salem IM, Hegazy WAH, Nazeih SI. Thymoquinone is a natural antibiofilm and pathogenicity attenuating agent in Pseudomonas aeruginosa. Front Cell Infect Microbiol 2024; 14:1382289. [PMID: 38638827 PMCID: PMC11024287 DOI: 10.3389/fcimb.2024.1382289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 03/08/2024] [Indexed: 04/20/2024] Open
Abstract
Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due to their high rate of resistance as listed by WHO. P. aeruginosa can result in many nosocomial infections especially in individuals with compromised immune systems. Attenuating virulence factors by interference with quorum sensing (QS) systems is a promising approach to treat P. aeruginosa-resistant infections. Thymoquinone is a natural compound isolated from Nigella sativa (black seed) essential oil. In this study, the minimum inhibitory concentration of thymoquinone was detected followed by investigating the antibiofilm and antivirulence activities of the subinhibitory concentration of thymoquinone against P. aeruginosa PAO1. The effect of thymoquinone on the expression of QS genes was assessed by quantitative real-time PCR, and the protective effect of thymoquinone against the pathogenesis of PAO1 in mice was detected by the mouse survival test. Thymoquinone significantly inhibited biofilm, pyocyanin, protease activity, and swarming motility. At the molecular level, thymoquinone markedly downregulated QS genes lasI, lasR, rhlI, and rhlR. Moreover, thymoquinone could protect mice from the pathologic effects of P. aeruginosa increasing mouse survival from 20% to 100%. In conclusion, thymoquinone is a promising natural agent that can be used as an adjunct therapeutic agent with antibiotics to attenuate the pathogenicity of P. aeruginosa.
Collapse
Affiliation(s)
- Mohammed W. Al-Rabia
- Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hani Z. Asfour
- Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
- Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Wesam H. Abdulaal
- Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Tarek S. Ibrahim
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hisham A. Abbas
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Ibrahim M. Salem
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, Assiut, Egypt
| | - Wael A. H. Hegazy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
- Pharmacy Program, Department of Pharmaceutical Sciences, Oman College of Health Sciences, Muscat, Oman
| | - Shaimaa I. Nazeih
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| |
Collapse
|
|
10
|
Datta S, Nag S, Roy DN. Biofilm-producing antibiotic-resistant bacteria in Indian patients: a comprehensive review. Curr Med Res Opin 2024; 40:403-422. [PMID: 38214582 DOI: 10.1080/03007995.2024.2305241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 01/10/2024] [Indexed: 01/13/2024]
Abstract
For the past few years, microbial biofilms have been emerging as a significant threat to the modern healthcare system, and their prevalence and antibiotic resistance threat gradually increase daily among the human population. The biofilm has a remarkable impact in the field of infectious diseases, in particular healthcare-associated infections related to indwelling devices such as catheters, implants, artificial heart valves, and prosthetic joints. Bacterial biofilm potentially adheres to any biotic or abiotic surfaces that give specific shelter to the microbial community, making them less susceptible to many antimicrobial agents and even resistant to the immune cells of animal hosts. Around thirty clinical research reports available in PUBMED have been considered to establish the occurrence of biofilm-forming bacteria showing resistance against several regular antibiotics prescribed against infection by clinicians among Indian patients. After the extensive literature review, our observation exhibits a high predominance of biofilm formation among bacteria such as Escherichia sp., Streptococcus sp., Staphylococcus sp., and Pseudomonas sp., those are the most common biofilm-producing antibiotic-resistant bacteria among Indian patients with urinary tract infections and/or catheter-related infections, respiratory tract infections, dental infections, skin infections, and implant-associated infections. This review demonstrates that biofilm-associated bacterial infections constantly elevate in several pathological conditions along with the enhancement of the multi-drug resistance phenomenon.
Collapse
Affiliation(s)
- Susmita Datta
- Department of Chemical Engineering, National Institute of Technology, Agartala, Tripura, India
| | - Soma Nag
- Department of Chemical Engineering, National Institute of Technology, Agartala, Tripura, India
| | - Dijendra Nath Roy
- Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
| |
Collapse
|
|
11
|
Chadha J, Thakur N, Chhibber S, Harjai K. A comprehensive status update on modification of foley catheter to combat catheter-associated urinary tract infections and microbial biofilms. Crit Rev Microbiol 2024; 50:168-195. [PMID: 36651058 DOI: 10.1080/1040841x.2023.2167593] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/01/2022] [Accepted: 01/09/2023] [Indexed: 01/19/2023]
Abstract
Present-day healthcare employs several types of invasive devices, including urinary catheters, to improve medical wellness, the clinical outcome of disease, and the quality of patient life. Among urinary catheters, the Foley catheter is most commonly used in patients for bladder drainage and collection of urine. Although such devices are very useful for patients who cannot empty their bladder for various reasons, they also expose patients to catheter-associated urinary tract infections (CAUTIs). Catheter provides an ideal surface for bacterial colonization and biofilm formation, resulting in persistent bacterial infection and severe complications. Hence, rigorous efforts have been made to develop catheters that harbour antimicrobial and anti-fouling properties to resist colonization by bacterial pathogens. In this regard, catheter modification by surface functionalization, impregnation, blending, or coating with antibiotics, bioactive compounds, and nanoformulations have proved to be effective in controlling biofilm formation. This review attempts to illustrate the complications associated with indwelling Foley catheters, primarily focussing on challenges in fighting CAUTI, catheter colonization, and biofilm formation. In this review, we also collate scientific literature on catheter modification using antibiotics, plant bioactive components, bacteriophages, nanoparticles, and studies demonstrating their efficacy through in vitro and in vivo testing.
Collapse
Affiliation(s)
- Jatin Chadha
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Navdisha Thakur
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Sanjay Chhibber
- Department of Microbiology, Panjab University, Chandigarh, India
| | - Kusum Harjai
- Department of Microbiology, Panjab University, Chandigarh, India
| |
Collapse
|
|
12
|
Kwak Y, Kim HG, Seok J, Kim S, Kim EM, Kim A. The Critical Role of Intracellular Bacterial Communities in Uncomplicated Recurrent Urinary Cystitis: A Comprehensive Review of Detection Methods and Diagnostic Potential. Int Neurourol J 2024; 28:4-10. [PMID: 38569615 PMCID: PMC10990762 DOI: 10.5213/inj.2448066.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 03/06/2024] [Indexed: 04/05/2024] Open
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are particularly prevalent in women. Recurrent UTIs significantly diminish quality of life due to their symptoms and frequent relapses. Patients often experience immediate relapse following slightly strenuous activities or intense psychological stress. In this review, we explore why infections persist despite the advent of various treatments and suggest strategies to manage recurrent cystitis by targeting the mechanisms of adhesion and infection. Vitamin D levels and the expression of neutrophil gelatinase-associated lipocalin are linked to the recurrence of UTIs. During a UTI, bacteria employ adhesins to invade the urinary tract, adhere to urothelial cells, and then penetrate these cells, where they rapidly multiply to establish intracellular bacterial communities. Bacteria can also form quiescent intracellular reservoirs that escape immune responses and antibiotic treatments, leading to recurrence under certain conditions. The surface proteins of bacteria and D-mannose are crucial in the adhesion of bacteria to the urothelium. Understanding these processes provides valuable insights into potential therapeutic approaches that focus on preventing bacterial attachment and cluster formation. By disrupting the ability of bacteria to adhere to and form clusters on cells, we can better manage recurrent UTIs and improve patient outcomes.
Collapse
Affiliation(s)
- Yeonjoo Kwak
- Department of Stem Cell & Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
| | - Hyeong Gon Kim
- Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Jaekwon Seok
- Department of Stem Cell & Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea
| | - Sehwan Kim
- Department of Biomedical Engineering, School of Medicine, Dankook University, Cheonan, Korea
| | - Eun-Mee Kim
- Department of Paramedicine, Korea Nazarene University, Cheonan, Korea
| | - Aram Kim
- Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
- University of California, Irvine, Beckman Laser Institute and Medical Clinic, Irvine, CA, USA
| |
Collapse
|
|
13
|
Kumaran D, Ramirez-Arcos S. Sebum Components Dampen the Efficacy of Skin Disinfectants against Cutibacterium acnes Biofilms. Microorganisms 2024; 12:271. [PMID: 38399675 PMCID: PMC10891977 DOI: 10.3390/microorganisms12020271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024] Open
Abstract
At Canadian Blood Services, despite the use of 2% chlorhexidine and 70% isopropyl alcohol (standard disinfectant, SD) prior to venipuncture, Cutibacterium acnes evades eradication and is a major contaminant of platelet concentrates (PCs). Since C. acnes forms bacterial aggregates known as biofilms in the sebaceous niches of the skin, this study aimed to assess whether sebum-like components impact disinfectant efficacy against C. acnes leading to its dominance as a PC contaminant. C. acnes mono-species and dual-species biofilms (C. acness and a transfusion-relevant Staphylococcus aureus isolate) were formed in the presence and absence of sebum-like components and exposed to SD, a hypochlorous acid-based disinfectant (Clinisept+, CP), or a combination of both disinfectants to assess disinfectant efficacy. Our data indicate that sebum-like components significantly reduce the disinfectant efficacy of all disinfectant strategies tested against C. acnes in both biofilm models. Furthermore, though none of the disinfectants led to bacterial eradication, the susceptibility of C. acnes to disinfectants was heightened in an isolate-dependent manner when grown in the presence of S. aureus. The reduction of skin disinfection efficacy in the presence of sebum may contribute to the overrepresentation of C. acnes as a PC contaminant and highlights the need for improved disinfection strategies.
Collapse
Affiliation(s)
- Dilini Kumaran
- Innovation & Portfolio Management, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada;
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | - Sandra Ramirez-Arcos
- Innovation & Portfolio Management, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada;
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| |
Collapse
|
|
14
|
Gliźniewicz M, Miłek D, Olszewska P, Czajkowski A, Serwin N, Cecerska-Heryć E, Dołęgowska B, Grygorcewicz B. Advances in bacteriophage-mediated strategies for combating polymicrobial biofilms. Front Microbiol 2024; 14:1320345. [PMID: 38249486 PMCID: PMC10797108 DOI: 10.3389/fmicb.2023.1320345] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/04/2023] [Indexed: 01/23/2024] Open
Abstract
Bacteria and fungi tend to coexist within biofilms instead of in planktonic states. Usually, such communities include cross-kingdom microorganisms, which make them harder to remove from abiotic surfaces or infection sites. Additionally, the produced biofilm matrix protects embedded microorganisms from antibiotics, disinfectants, or the host immune system. Therefore, classic therapies based on antibiotics might be ineffective, especially when multidrug-resistant bacteria are causative factors. The complexities surrounding the eradication of biofilms from diverse surfaces and the human body have spurred the exploration of alternative therapeutic modalities. Among these options, bacteriophages and their enzymatic counterparts have emerged as promising candidates, either employed independently or in synergy with antibiotics and other agents. Phages are natural bacteria killers because of mechanisms of action that differ from antibiotics, phages might answer worldwide problems with bacterial infections. In this review, we report the attempts to use bacteriophages in combating polymicrobial biofilms in in vitro studies, using different models, including the therapeutical use of phages. In addition, we sum up the advantages, disadvantages, and perspectives of phage therapy.
Collapse
Affiliation(s)
- Marta Gliźniewicz
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Dominika Miłek
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Patrycja Olszewska
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Artur Czajkowski
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Natalia Serwin
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Elżbieta Cecerska-Heryć
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Barbara Dołęgowska
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Bartłomiej Grygorcewicz
- Faculty of Pharmacy, Medical Biotechnology and Laboratory Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland
- Department of Chemical Technology and Engineering, Institute of Chemical Engineering and Environmental Protection Processes, West Pomeranian University of Technology, Szczecin, Poland
| |
Collapse
|
|
15
|
Chung FY, Lin YZ, Huang CR, Huang KW, Chen YF. Crosslinking kiwifruit-derived DNA with natural aromatic aldehydes generates membranolytic antibacterial nanogels. Int J Biol Macromol 2024; 255:127947. [PMID: 37951422 DOI: 10.1016/j.ijbiomac.2023.127947] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 10/14/2023] [Accepted: 10/31/2023] [Indexed: 11/14/2023]
Abstract
Improper use of antibiotics has led to the global rise of drug-resistant biofilm bacteria. Thus, researchers have been increasingly interested in green materials that are highly biocompatible and have low toxicity. Here, nanogels (NGs) with imine bonds were synthesized by crosslinking kiwifruit-derived DNA's primary amine and aromatic aldehydes (cuminaldehyde, p-anisaldehyde, or vanillin) under water-in-hexane emulsion processes. Transmission electron microscope showed that the NGs had spherical geometry with an average particle size ranging from 40 to 140 nm and that the zeta potential indicated a negative charge. Additionally, the DNA-aromatic aldehyde NGs showed low cytotoxicity toward normal cell organoids and human RBCs in cell viability tests. These NGs were also tested against four pathogenic bacteria for various assays. DNA-vanillin (DNA-VA) NGs exhibited significant antibacterial effects against bacteria with very low inhibitory concentrations as seen in a minimum inhibitory concentration assay. Scanning electron microscope observation revealed that the bacteria were deformed, and immunoblotting detected intracellular groEL protein expression. In agreement with these results, DNA-aromatic aldehyde NGs successfully protected C. elegans from P. aeruginosa-induced lethality. These DNA NGs provided a multivalent 3D space for antibacterial aromatic aldehydes to tether, enhancing their interaction with the bacterial wall. These results offer a new direction for the development of novel antibiotics in the future.
Collapse
Affiliation(s)
- Fang-Yu Chung
- Master Program in Biomedicine, National Taitung University, No. 684, Section 1, Zhonghua Rd., Taitung 95092, Taiwan
| | - Yi-Zhen Lin
- Master Program in Biomedicine, National Taitung University, No. 684, Section 1, Zhonghua Rd., Taitung 95092, Taiwan
| | - Cheng-Rung Huang
- Department of Biochemistry and Molecular Biology, National Cheng Kung University, No. 1, University Rd., East Dist., Tainan 70101, Taiwan
| | - Kuan-Wen Huang
- Master Program in Biomedicine, National Taitung University, No. 684, Section 1, Zhonghua Rd., Taitung 95092, Taiwan
| | - Yu-Fon Chen
- Master Program in Biomedicine, National Taitung University, No. 684, Section 1, Zhonghua Rd., Taitung 95092, Taiwan.
| |
Collapse
|
|
16
|
Nejad MK, Hasani A, Soofiyani SR, Nahandi MZ, Hasani A. Aptitude of Uropathogenic Escherichia coli in Renal Transplant Recipients: A Comprehensive Review on Characteristic Features, and Production of Extended Spectrum β-Lactamase. Curr Microbiol 2023; 80:382. [PMID: 37864769 DOI: 10.1007/s00284-023-03476-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 09/05/2023] [Indexed: 10/23/2023]
Abstract
Urinary tract infection is the most common infection in almost half of the renal transplant patients. The development of UTI in these patients may progress to bacteremia, acute T cell-mediated rejection, impaired allograft function, or allograft loss, along with the increased risk of hospitalization and death. Among various pathogens implicated, Uropathogenic E. coli (UPEC), especially sequence type 131 (ST131), is the most virulent and multidrug-resistant pathogen. High antimicrobial resistance to most β-lactam antibiotics, mediated by extended spectrum β-lactamases (ESBLs) produced by UPEC, is a challenge in the clinical management of UTIs in kidney transplant recipients. Indeed, multidrug resistance to β-lactam antibiotics is a direct consequence of ESBL production. Resistance to other antibiotics such as aminoglycosides, fluoroquinolones, and trimethoprim-sulphamethoxazole has also been reported in ESBLs-producing UPEC, which reduces the therapeutic options, rising healthcare-associated costs and subsequently leads to renal failure or even graft loss. In this review, we aimed to discuss the post-transplant risk factors of UTI, UPEC virulence factors (VF), and the related factors including quorum sensing, and stress resistance genes. Furthermore, we searched for the current treatment strategies and some of the alternate approaches proposed as therapeutic options that may affirm the treatment of ESBL-producing UPEC.
Collapse
Affiliation(s)
- Masoomeh Kashef Nejad
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alka Hasani
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Saiedeh Razi Soofiyani
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Zaare Nahandi
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Akbar Hasani
- Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
17
|
Bouassida K, Marzouk M, Nouir S, Ghammem R, Sahtout W, Ghardallou M, Fathallah N, Boukadida J, Jaidane M, Slim R, Zaïri A. Analysis of Pathogens of Urinary Tract Infections Associated with Indwelling Double-J Stents and Their Susceptibility to Globularia alypum. Pharmaceutics 2023; 15:2496. [PMID: 37896256 PMCID: PMC10609942 DOI: 10.3390/pharmaceutics15102496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/06/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Ureteral double-J stents are frequently used to prevent urinary obstruction. They can develop bacterial colonization and encrustation, which leads to persistent infections that seldom respond to antibiotic treatment. Thus, the goal of this study was to evaluate the local spectrum of bacterial pathogens and their susceptibility to natural compounds. A total of 59 double-J ureteral stents from 59 consecutive patients were examined. The samples were inoculated on agar culture mediums. Extracts of Globularia alypum L. were evaluated for their antibacterial activity with the diffusion and broth dilution methods; for antibiofilm activity, the crystal violet assay was used. The identification and the quantification of the different constituents of extracts were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Bacterial growth was found in three patients (5.1%). Enterococcus faecalis (1.7%), Acinetobacter baumanii (1.7%), and Pseudomonas putida (1.7%) strains were more commonly detected. They were resistant to several common antibiotics. All extracts presented several components, mainly nepetin-7-glucoside and trans-ferulic-acid, and they had antibacterial activity (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties, especially against Acinetobacter baumanii. The results achieved confirm the important role of this plant as a source of therapeutic activities.
Collapse
Affiliation(s)
| | - Manel Marzouk
- Laboratory of Microbiology, Hospital Farhat Hached, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia; (M.M.); (J.B.)
| | - Sahar Nouir
- Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia;
| | - Rim Ghammem
- Department of Epidemiology and Preventive Medicine, University of Sousse, Sousse 4002, Tunisia;
| | - Wissal Sahtout
- Nephrology Department, Sahloul Hospital, Sousse 4054, Tunisia;
| | - Meriam Ghardallou
- Department of Community Medicine, Research Laboratory LR12ES03, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia;
| | - Neila Fathallah
- Department of Clinical Pharmacology, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia; (N.F.); (R.S.)
| | - Jalel Boukadida
- Laboratory of Microbiology, Hospital Farhat Hached, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia; (M.M.); (J.B.)
| | - Mehdi Jaidane
- Urology Department, Sahloul Hospital, Sousse 4054, Tunisia; (K.B.); (M.J.)
| | - Raoudha Slim
- Department of Clinical Pharmacology, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia; (N.F.); (R.S.)
| | - Amira Zaïri
- Laboratory of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, Sousse 4002, Tunisia;
| |
Collapse
|
|
18
|
Melnick D, Talley AK, Gupta VK, Critchley IA, Eckburg PB, Hamed KA, Bhatt N, Moore G, Austin D, Rubino CM, Bhavnani SM, Ambrose PG. Impact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections. Antimicrob Agents Chemother 2023; 67:e0053523. [PMID: 37768311 PMCID: PMC10583661 DOI: 10.1128/aac.00535-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 07/16/2023] [Indexed: 09/29/2023] Open
Abstract
The clinical relevance of bacteriuria following antibiotic treatment of complicated urinary tract infections in clinical trials remains controversial. We evaluated the impact of urine pharmacokinetics on the timing of recurrent bacteriuria in a recently completed trial that compared oral tebipenem pivoxil hydrobromide to intravenous ertapenem. The urinary clearance and urine dwell time of ertapenem were prolonged relative to tebipenem and were associated with a temporal difference in the repopulation of bladder urine with bacteria following treatment, potentially confounding the assessment of efficacy.
Collapse
Affiliation(s)
- David Melnick
- Spero Therapeutics, Inc., Cambridge, Massachusetts, USA
| | | | | | | | | | | | | | - Gary Moore
- Moore Computing Services, Inc., Little Rock, Arkansas, USA
| | | | | | - Sujata M. Bhavnani
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| | - Paul G. Ambrose
- Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA
| |
Collapse
|
|
19
|
Liu T, Zhai Y, Jeong KC. Advancing understanding of microbial biofilms through machine learning-powered studies. Food Sci Biotechnol 2023; 32:1653-1664. [PMID: 37780593 PMCID: PMC10533454 DOI: 10.1007/s10068-023-01415-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/26/2023] [Accepted: 08/07/2023] [Indexed: 10/03/2023] Open
Abstract
Microbial biofilms are prevalent in various environments and pose significant challenges to food safety and public health. The biofilms formed by pathogens can cause food spoilage, foodborne illness, and infectious diseases, which are difficult to treat due to their enhanced antimicrobial resistance. While the composition and development of biofilms have been widely studied, their profound impact on food, the food industry, and public health has not been sufficiently recapitulated. This review aims to provide a comprehensive overview of microbial biofilms in the food industry and their implication on public health. It highlights the existence of biofilms along the food-producing chains and the underlying mechanisms of biofilm-associated diseases. Furthermore, this review thoroughly summarizes the enhanced understanding of microbial biofilms achieved through machine learning approaches in biofilm research. By consolidating existing knowledge, this review intends to facilitate developing effective strategies to combat biofilm-associated infections in both the food industry and public health.
Collapse
Affiliation(s)
- Ting Liu
- Emerging Pathogens Institute, University of Florida, 2055 Mowry Rd, Gainesville, FL 32610 USA
- Department of Animal Sciences, University of Florida, 2250 Shealy Dr, Gainesville, FL 32608 USA
| | - Yuting Zhai
- Emerging Pathogens Institute, University of Florida, 2055 Mowry Rd, Gainesville, FL 32610 USA
- Department of Animal Sciences, University of Florida, 2250 Shealy Dr, Gainesville, FL 32608 USA
| | - Kwangcheol Casey Jeong
- Emerging Pathogens Institute, University of Florida, 2055 Mowry Rd, Gainesville, FL 32610 USA
- Department of Animal Sciences, University of Florida, 2250 Shealy Dr, Gainesville, FL 32608 USA
| |
Collapse
|
|
20
|
Rastegar E, Malekzadegan Y, Khashei R, Hadi N. Quinolone resistance and biofilm formation capability of uropathogenic Escherichia coli isolates from an Iranian inpatients' population. Mol Biol Rep 2023; 50:8073-8079. [PMID: 37540453 DOI: 10.1007/s11033-023-08704-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 07/20/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND Uropathogenic Escherichia coli (UPEC) is a major pathogen of the urinary tract infection (UTI), and biofilm formation is crucial as it facilitates the colonization in the urinary tract. We aimed to investigate the antibiotic susceptibility pattern, biofilm formation capability, distribution of quinolone resistance genes, and phylogenetic groups among UPEC isolates from an Iranian inpatients' community. METHODS AND RESULTS A collection of 126 UPEC obtained from hospitalized patients with symptomatic UTI at 3 teaching hospitals during 2016 were included. Antibiogram of all isolates against quinolone and fluoroquinolones was performed using the disk diffusion method. Phylogenetic groups and qnr A, B, and S genes were assessed by PCR. Susceptibility pattern showed that more than 50% and 81% of the isolates were resistant to fluoroquinolones and quinolones, correspondingly. The frequency of qnrS and qnrB genes was 22% and 13.5%, correspondingly. Our result indicated no significant association between the presence of fluoroquinolone genes and antibiotic resistance to them. The frequent common phylogroup was B2 (84.1%), followed by D (10.3%), A (3.2%) and B1 (2.4%) groups. Indeed, 80.2% of the isolates were biofilm producers, so that 42.1%, 16.7% and 21.4% of them were classified as weak, moderate and strong producers, respectively. CONCLUSIONS Our results showed considerable fluoroquinolone and quinolone resistance among UPEC along with a remarkable rate of biofilm-producing isolates from symptomatic hospitalized patients, making them a serious health concern in the region. This survey highlights the need for awareness on quinolone resistance and careful prescription of them by physicians.
Collapse
Affiliation(s)
- Elham Rastegar
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Reza Khashei
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Nahal Hadi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
21
|
Wang S, Zhao Y, Breslawec AP, Liang T, Deng Z, Kuperman LL, Yu Q. Strategy to combat biofilms: a focus on biofilm dispersal enzymes. NPJ Biofilms Microbiomes 2023; 9:63. [PMID: 37679355 PMCID: PMC10485009 DOI: 10.1038/s41522-023-00427-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 08/15/2023] [Indexed: 09/09/2023] Open
Abstract
Bacterial biofilms, which consist of three-dimensional extracellular polymeric substance (EPS), not only function as signaling networks, provide nutritional support, and facilitate surface adhesion, but also serve as a protective shield for the residing bacterial inhabitants against external stress, such as antibiotics, antimicrobials, and host immune responses. Biofilm-associated infections account for 65-80% of all human microbial infections that lead to serious mortality and morbidity. Tremendous effort has been spent to address the problem by developing biofilm-dispersing agents to discharge colonized microbial cells to a more vulnerable planktonic state. Here, we discuss the recent progress of enzymatic eradicating strategies against medical biofilms, with a focus on dispersal mechanisms. Particularly, we review three enzyme classes that have been extensively investigated, namely glycoside hydrolases, proteases, and deoxyribonucleases.
Collapse
Affiliation(s)
- Shaochi Wang
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China
| | - Yanteng Zhao
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China
| | - Alexandra P Breslawec
- Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20740, USA
| | - Tingting Liang
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University Jinming Campus, 475004, Kaifeng, Henan, China
| | - Zhifen Deng
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China
| | - Laura L Kuperman
- Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20740, USA.
- Mirimus Inc., 760 Parkside Avenue, Brooklyn, NY, 11226, USA.
| | - Qiuning Yu
- Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.
| |
Collapse
|
|
22
|
Mishra RAK, Muthukaliannan GK, Rathinasabapathi P. Effects of Flavonoids and Antibiotics Combination on Preformed Biofilms and Small RNA of Staphylococcus aureus. Indian J Microbiol 2023; 63:307-316. [PMID: 37781018 PMCID: PMC10533456 DOI: 10.1007/s12088-023-01086-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 07/24/2023] [Indexed: 10/03/2023] Open
Abstract
Antibiotic resistance of Staphylococcus aureus has considerably increased among non-clinical or asymptomatic individuals. The formation of biofilms denies antimicrobial access to its targets present on the surface and inside the cell. The present study tested the effect of the combination of flavonoids and antibiotics over the preformed biofilms of S. aureus. The eradication of the preformed biofilms was analyzed using the crystal violet method. It has shown that 2500 µg mL-1 Rutin and 100 µg mL-1 Erythromycin (MIC Concentration) combination efficiently reduced the growth of the cells, which were adhered to the surfaces forming the biofilms. Fluorescence microscopic analysis indicated that the Rutin and Erythromycin (MIC value) combinations could eradicate the preformed biofilm cells more efficiently than other combinations. We found that the flavonoids and antibiotics with MIC concentration show a significant effect over the preformed biofilms cells of S. aureus. In addition, the semi-quantitative real-time PCR analysis for the sRNAs under the treatment of Rutin and Erythromycin combinations showed that few small RNAs expression (SprF, SprG, ArtR, Teg49, Teg41, and RNAIII) are getting downregulated upon the treatment; but again recovers with the incubation time interval increases. Combinations have a significant effect on Teg49 where there is a very faint intensity of the band, but for other small RNAs, there is an irregular pattern on the gel image. It has been concluded that at the initial period of incubation, the combinations have an effect on all the sRNAs but once the incubation increases, the effects have been slowly decreasing. It has been concluded that the combination has been able to reduce the doubling time of S. aureus upon treatment. Whereas, the small RNAs used in the study can be further evaluated for expression profiling through qRT-PCT. Graphical abstract
Collapse
Affiliation(s)
- Rudra Awdhesh Kumar Mishra
- School of Biosciences and Technology, Vellore Institute of Technology, Katpadi, Vellore, 632014 India
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, 603203 Tamil Nadu India
| | | | - Pasupathi Rathinasabapathi
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, 603203 Tamil Nadu India
| |
Collapse
|
|
23
|
Bai Y, Wang Y, Kang M, Gabe CM, Srirangapatanam S, Edwards A, Stoller M, Green SJ, Aloni S, Tamura N, Beniash E, Hardt M, Ho SP. Organic Matrix Derived from Host-Microbe Interplay Contributes to Pathological Renal Biomineralization. ACS NANOSCIENCE AU 2023; 3:335-346. [PMID: 37601921 PMCID: PMC10436370 DOI: 10.1021/acsnanoscienceau.2c00060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 05/26/2023] [Accepted: 05/26/2023] [Indexed: 08/22/2023]
Abstract
Matrix stones are a rare form of kidney stones. They feature a high percentage of hydrogel-like organic matter, and their formation is closely associated with urinary tract infections. Herein, comprehensive materials and biochemical approaches were taken to map the organic-inorganic interface and gather insights into the host-microbe interplay in pathological renal biomineralization. Surgically extracted soft and slimy matrix stones were examined using micro-X-ray computed tomography and various microspectroscopy techniques. Higher-mineral-density laminae were positive for calcium-bound Alizarin red. Lower-mineral-density laminae revealed periodic acid-Schiff-positive organic filamentous networks of varied thickness. These organic filamentous networks, which featured a high polysaccharide content, were enriched with zinc, carbon, and sulfur elements. Neutrophil extracellular traps (NETs) along with immune response-related proteins, including calprotectin, myeloperoxidase, CD63, and CD86, also were identified in the filamentous networks. Expressions of NETs and upregulation of polysaccharide-rich mucin secretion are proposed as a part of the host immune defense to "trap" pathogens. These host-microbe derived organic matrices can facilitate heterogeneous nucleation and precipitation of inorganic particulates, resulting in macroscale aggregates known as "matrix stones". These insights into the plausible aggregation of constituents through host-microbe interplay underscore the unique "double-edged sword" effect of the host immune response to pathogens and the resulting renal biominerals.
Collapse
Affiliation(s)
- Yushi Bai
- Department
of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States
| | - Yongmei Wang
- Department
of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States
| | - Misun Kang
- Department
of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States
| | - Claire M. Gabe
- Department
of Oral and Craniofacial Sciences, School of Dentistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
| | - Sudarshan Srirangapatanam
- Department
of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States
- College
of Medicine, University of Central Florida, Orlando, Florida 32827, United States
| | - Austin Edwards
- Biological
Imaging Development Center, University of
California San Francisco, San Francisco, California 94143, United States
| | - Marshall Stoller
- Department
of Urology, School of Medicine, University
of California San Francisco, San Francisco, California 94143, United States
| | - Stefan J. Green
- Department
of Internal Medicine, Division of Infectious Diseases, Rush Medical
College, Rush University, Chicago, Illinois 60612, United States
| | - Shaul Aloni
- The
Molecular Foundry, Lawrence Berkeley National
Laboratory, Berkeley, California 94720, United States
| | - Nobumichi Tamura
- Advanced
Light Source, Lawrence Berkeley National
Laboratory, Berkeley, California 94720, United States
| | - Elia Beniash
- Department
of Oral and Craniofacial Sciences, School of Dentistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
| | - Markus Hardt
- Center
for Salivary Diagnostics, The Forsyth Institute, Cambridge, Massachusetts 02142, United States
- Department
of Developmental Biology, Harvard School
of Dental Medicine, Boston, Massachusetts 02115, United States
| | - Sunita P. Ho
- Department
of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States
- Department
of Urology, School of Medicine, University
of California San Francisco, San Francisco, California 94143, United States
| |
Collapse
|
|
24
|
Ali Y, Inusa I, Sanghvi G, Mandaliya V, Bishoyi AK. The current status of phage therapy and its advancement towards establishing standard antimicrobials for combating multi drug-resistant bacterial pathogens. Microb Pathog 2023:106199. [PMID: 37336428 DOI: 10.1016/j.micpath.2023.106199] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/06/2023] [Accepted: 06/09/2023] [Indexed: 06/21/2023]
Abstract
Phage therapy; a revived antimicrobial weapon, has great therapeutic advantages with the main ones being its ability to eradicate multidrug-resistant pathogens as well as selective toxicity, which ensures that beneficial microbiota is not harmed, unlike antibiotics. These therapeutic properties make phage therapy a novel approach for combating resistant pathogens. Since millions of people across the globe succumb to multidrug-resistant infections, the implementation of phage therapy as a standard antimicrobial could transform global medicine as it offers greater therapeutic advantages than conventional antibiotics. Although phage therapy has incomplete clinical data, such as a lack of standard dosage and the ideal mode of administration, the conducted clinical studies report its safety and efficacy in some case studies, and therefore, this could lessen the concerns of its skeptics. Since its discovery, the development of phage therapeutics has been in a smooth progression. Concerns about phage resistance in populations of pathogenic bacteria are raised when bacteria are exposed to phages. Bacteria can use restriction-modification, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) defense, or mutations in the phage receptors to prevent phage invasion. Phage resistance, however, is often costly for the bacteria and may lead to a reduction in its virulence. The ongoing competition between bacteria and phage, on the other hand, ensures the emergence of phage strains that have evolved to infect resistant bacteria. A phage can quickly adapt by altering one or more aspects of its mode of infection, evading a resistance mechanism through genetic modifications, or directly thwarting the CRISPR-Cas defense. Using phage-bacterium coevolution as a technique could be crucial in the development of phage therapy as well. Through its recent advancement, gene-editing tools such as CRISPR-Cas allow the bioengineering of phages to produce phage cocktails that have broad spectrum activities, which could maximize the treatment's efficacy. This review presents the current state of phage therapy and its progression toward establishing standard medicine for combating antibiotic resistance. Recent clinical trials of phage therapy, some important case studies, and other ongoing clinical studies of phage therapy are all presented in this review. Furthermore, the recent advancement in the development of phage therapeutics, its application in various sectors, and concerns regarding its implementation are also highlighted here. Phage therapy has great potential and could help the fight against drug-resistant bacterial pathogens.
Collapse
Affiliation(s)
- Yussuf Ali
- Department of Microbiology, Marwadi University, Gujarat, India
| | - Ibrahim Inusa
- Department of Information Technology, Marwadi University, Gujarat, India
| | - Gaurav Sanghvi
- Department of Microbiology, Marwadi University, Gujarat, India
| | | | | |
Collapse
|
|
25
|
Rajab AAH, Hegazy WAH. What’s old is new again: Insights into diabetic foot microbiome. World J Diabetes 2023; 14:680-704. [PMID: 37383589 PMCID: PMC10294069 DOI: 10.4239/wjd.v14.i6.680] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/20/2023] [Accepted: 04/10/2023] [Indexed: 06/14/2023] Open
Abstract
Diabetes is a chronic disease that is considered one of the most stubborn global health problems that continues to defy the efforts of scientists and physicians. The prevalence of diabetes in the global population continues to grow to alarming levels year after year, causing an increase in the incidence of diabetes complications and health care costs all over the world. One major complication of diabetes is the high susceptibility to infections especially in the lower limbs due to the immunocompromised state of diabetic patients, which is considered a definitive factor in all cases. Diabetic foot infections continue to be one of the most common infections in diabetic patients that are associated with a high risk of serious complications such as bone infection, limb amputations, and life-threatening systemic infections. In this review, we discussed the circumstances associated with the high risk of infection in diabetic patients as well as some of the most commonly isolated pathogens from diabetic foot infections and the related virulence behavior. In addition, we shed light on the different treatment strategies that aim at eradicating the infection.
Collapse
Affiliation(s)
- Azza A H Rajab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagzig 44511, Egypt
| | - Wael A H Hegazy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagzig 44511, Egypt
| |
Collapse
|
|
26
|
Čeprnja M, Hadžić E, Oros D, Melvan E, Starcevic A, Zucko J. Current Viewpoint on Female Urogenital Microbiome-The Cause or the Consequence? Microorganisms 2023; 11:1207. [PMID: 37317181 PMCID: PMC10224287 DOI: 10.3390/microorganisms11051207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/01/2023] [Accepted: 05/03/2023] [Indexed: 06/16/2023] Open
Abstract
An increasing amount of evidence implies that native microbiota is a constituent part of a healthy urinary tract (UT), making it an ecosystem on its own. What is still not clear is whether the origin of the urinary microbial community is the indirect consequence of the more abundant gut microbiota or a more distinct separation exists between these two systems. Another area of uncertainty is the existence of a link between the shifts in UT microbial composition and both the onset and persistence of cystitis symptoms. Cystitis is one of the most common reasons for antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of the majority of cystitis cases is a single pathogen overgrowth or a systemic disorder affecting the entire urinary microbiota. There is an increasing trend in studies monitoring changes and dynamics of UT microbiota, but this field of research is still in its infancy. Using NGS and bioinformatics, it is possible to obtain microbiota taxonomic profiles directly from urine samples, which can provide a window into microbial diversity (or the lack of) underlying each patient's cystitis symptoms. However, while microbiota refers to the living collection of microorganisms, an interchangeably used term microbiome referring to the genetic material of the microbiota is more often used in conjunction with sequencing data. It is this vast amount of sequences, which are truly "Big Data", that allow us to create models that describe interactions between different species contributing to an UT ecosystem, when coupled with machine-learning techniques. Although in a simplified predator-prey form these multi-species interaction models have the potential to further validate or disprove current beliefs; whether it is the presence or the absence of particular key players in a UT microbial ecosystem, the exact cause or consequence of the otherwise unknown etiology in the majority of cystitis cases. These insights might prove to be vital in our ongoing struggle against pathogen resistance and offer us new and promising clinical markers.
Collapse
Affiliation(s)
- Marina Čeprnja
- Biochemical Laboratory, Special Hospital Agram, Polyclinic Zagreb, 10000 Zagreb, Croatia
| | - Edin Hadžić
- Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, Zagreb University, 10000 Zagreb, Croatia
| | - Damir Oros
- Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, Zagreb University, 10000 Zagreb, Croatia
| | - Ena Melvan
- Department of Biological Science, Faculty of Science, Macquarie University, Sydney, NSW 2109, Australia
| | - Antonio Starcevic
- Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, Zagreb University, 10000 Zagreb, Croatia
| | - Jurica Zucko
- Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, Zagreb University, 10000 Zagreb, Croatia
| |
Collapse
|
|
27
|
Codelia-Anjum A, Lerner LB, Elterman D, Zorn KC, Bhojani N, Chughtai B. Enterococcal Urinary Tract Infections: A Review of the Pathogenicity, Epidemiology, and Treatment. Antibiotics (Basel) 2023; 12:antibiotics12040778. [PMID: 37107140 PMCID: PMC10135011 DOI: 10.3390/antibiotics12040778] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/13/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
Urinary tract infections (UTIs) are among the most common causes of infections worldwide and can be caused by numerous uropathogens. Enterococci are Gram-positive, facultative anaerobic commensal organisms of the gastrointestinal tract that are known uropathogens. Enterococcus spp. has become a leading cause of healthcare associated infections, ranging from endocarditis to UTIs. In recent years, there has been an increase in multidrug resistance due to antibiotic misuse, especially in enterococci. Additionally, infections due to enterococci pose a unique challenge due to their ability to survive in extreme environments, intrinsic antimicrobial resistance, and genomic malleability. Overall, this review aims to highlight the pathogenicity, epidemiology, and treatment recommendations (according to the most recent guidelines) of enterococci.
Collapse
Affiliation(s)
- Alia Codelia-Anjum
- Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY 10065, USA
| | - Lori B Lerner
- Department of Urology, VA Boston Healthcare System, Boston, MA 02132, USA
| | - Dean Elterman
- Division of Urology, Department of Surgery, University Health Network, University of Toronto, Toronto, ON M5T 2SB, Canada
| | - Kevin C Zorn
- Division of Urology, Centre Hospitalier de l'Université de Monstréal, Montreal, QC H2X 0A9, Canada
| | - Naeem Bhojani
- Division of Urology, Centre Hospitalier de l'Université de Monstréal, Montreal, QC H2X 0A9, Canada
| | - Bilal Chughtai
- Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY 10065, USA
| |
Collapse
|
|
28
|
Truşcă BS, Gheorghe-Barbu I, Manea M, Ianculescu E, Barbu IC, Măruțescu LG, Dițu LM, Chifiriuc MC, Lazăr V. Snapshot of Phenotypic and Molecular Virulence and Resistance Profiles in Multidrug-Resistant Strains Isolated in a Tertiary Hospital in Romania. Pathogens 2023; 12:pathogens12040609. [PMID: 37111495 PMCID: PMC10145626 DOI: 10.3390/pathogens12040609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
A current major healthcare problem is represented by antibiotic resistance, mainly due to multidrug resistant (MDR) Gram negative bacilli (GNB), because of their extended spread both in hospital facilities and in the community's environment. The aim of this study was to investigate the virulence traits of Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa MDR, XDR, and PDR strains isolated from various hospitalized patients. These GNB strains were investigated for the presence of soluble virulence factors (VF), such as hemolysins, lecithinase, amylase, lipase, caseinase, gelatinase, and esculin hydrolysis, as well as for the presence of virulence genes encoding for VF involved in adherence (TC, fimH, and fimA), biofilm formation (algD, ecpRAB, mrkA, mrkD, ompA, and epsA), tissue destruction (plcH and plcN), and in toxin production (cnfI, hlyA, hlyD, and exo complex). All P. aeruginosa strains produced hemolysins; 90% produced lecithinase; and 80% harbored algD, plcH, and plcN genes. The esculin hydrolysis was detected in 96.1% of the K. pneumoniae strains, whereas 86% of them were positive for the mrkA gene. All of the A. baumannii strains produced lecithinase and 80% presented the ompA gene. A significant association was found between the number of VF and the XDR strains, regardless of the isolation sources. This study opens new research perspectives related to bacterial fitness and pathogenicity, and it provides new insights regarding the connection between biofilm formation, other virulence factors, and antibiotic resistance.
Collapse
Affiliation(s)
- Bianca Simona Truşcă
- Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
| | - Irina Gheorghe-Barbu
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050567 Bucharest, Romania
| | - Marina Manea
- Fundeni Clinical Institute, 022328 Bucharest, Romania
- Fundeni Clinical Institute, University of Medicine and Pharmacy "Carol Davila" Bucharest, 020021 Bucharest, Romania
| | | | - Ilda Czobor Barbu
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050567 Bucharest, Romania
| | - Luminița Gabriela Măruțescu
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050567 Bucharest, Romania
| | - Lia-Mara Dițu
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050567 Bucharest, Romania
| | - Mariana-Carmen Chifiriuc
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050567 Bucharest, Romania
- Romanian Academy, 050045 Bucharest, Romania
| | - Veronica Lazăr
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
| |
Collapse
|
|
29
|
Amante C, De Soricellis C, Luccheo G, Luccheo L, Russo P, Aquino RP, Del Gaudio P. Flogomicina: A Natural Antioxidant Mixture as an Alternative Strategy to Reduce Biofilm Formation. Life (Basel) 2023; 13:life13041005. [PMID: 37109533 PMCID: PMC10142241 DOI: 10.3390/life13041005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/07/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
The National Institute of Health has reported that approximately 80% of chronic infections are associated with biofilms, which are indicated as one of the main reasons for bacteria's resistance to antimicrobial agents. Several studies have revealed the role of N-acetylcysteine (NAC), in reducing biofilm formation induced by different microorganisms. A novel mixture made up of NAC and different natural ingredients (bromelain, ascorbic acid, Ribes nigrum, resveratrol, and pelargonium) has been developed in order to obtain a pool of antioxidants as an alternative strategy for biofilm reduction. The study has demonstrated that the mixture is able to significantly enhance NAC activity against different Gram-positive and Gram-negative bacteria. It has shown an increase in NAC permeation in vitro through an artificial fluid, moving from 2.5 to 8 μg/cm2 after 30 min and from 4.4 to 21.6 μg/cm2 after 180 min, and exhibiting a strongly fibrinolytic activity compared to the single components of the mixture. Moreover, this novel mixture has exhibited an antibiofilm activity against S aureus and the ability to reduce S. aureus growth by more than 20% in a time-killing assay, while on E. coli, and P. mirabilis, the growth was reduced by more than 80% compared to NAC. The flogomicina mixture has also been proven capable of reducing bacterial adhesion to abiotic surfaces of E.coli, by more than 11% concerning only the NAC. In combination with amoxicillin, it has been shown to significantly increase the drug's effectiveness after 14 days, offering a safe and natural way to reduce the daily dosage of antibiotics in prolonged therapies and consequently, reduce antibiotic resistance.
Collapse
Affiliation(s)
- Chiara Amante
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy
| | - Chiara De Soricellis
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy
| | - Gianni Luccheo
- Anvest Health s.r.l., Via Rosario Livatino, 84083 Castel San Giorgio, SA, Italy
| | - Luigi Luccheo
- Anvest Health s.r.l., Via Rosario Livatino, 84083 Castel San Giorgio, SA, Italy
| | - Paola Russo
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy
| | - Rita Patrizia Aquino
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy
| | - Pasquale Del Gaudio
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy
| |
Collapse
|
|
30
|
Zhao A, Sun J, Liu Y. Understanding bacterial biofilms: From definition to treatment strategies. Front Cell Infect Microbiol 2023; 13:1137947. [PMID: 37091673 PMCID: PMC10117668 DOI: 10.3389/fcimb.2023.1137947] [Citation(s) in RCA: 117] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 03/09/2023] [Indexed: 04/08/2023] Open
Abstract
Bacterial biofilms are complex microbial communities encased in extracellular polymeric substances. Their formation is a multi-step process. Biofilms are a significant problem in treating bacterial infections and are one of the main reasons for the persistence of infections. They can exhibit increased resistance to classical antibiotics and cause disease through device-related and non-device (tissue) -associated infections, posing a severe threat to global health issues. Therefore, early detection and search for new and alternative treatments are essential for treating and suppressing biofilm-associated infections. In this paper, we systematically reviewed the formation of bacterial biofilms, associated infections, detection methods, and potential treatment strategies, aiming to provide researchers with the latest progress in the detection and treatment of bacterial biofilms.
Collapse
Affiliation(s)
- Ailing Zhao
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Jiazheng Sun
- Department of Vasculocardiology, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Yipin Liu
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
- *Correspondence: Yipin Liu,
| |
Collapse
|
|
31
|
Lila ASA, Rajab AAH, Abdallah MH, Rizvi SMD, Moin A, Khafagy ES, Tabrez S, Hegazy WAH. Biofilm Lifestyle in Recurrent Urinary Tract Infections. LIFE (BASEL, SWITZERLAND) 2023; 13:life13010148. [PMID: 36676100 PMCID: PMC9865985 DOI: 10.3390/life13010148] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/27/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023]
Abstract
Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that offer protection and safe hiding, allowing bacteria to evade host defenses and hide from the reach of antibiotics. Inside biofilm communities, bacteria show an increased rate of horizontal gene transfer and exchange of resistance and virulence genes. Additionally, bacterial communication within the biofilm allows them to orchestrate the expression of virulence genes, which further cements the infestation and increases the invasiveness of the infection. These facts stress the necessity of continuously updating our information and understanding of the etiology, pathogenesis, and eradication methods of this growing public health concern. This review seeks to understand the role of biofilm formation in recurrent urinary tact infections by outlining the mechanisms underlying biofilm formation in different uropathogens, in addition to shedding light on some biofilm eradication strategies.
Collapse
Affiliation(s)
- Amr S. Abu Lila
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia
- Molecular Diagnostics and Personalized Therapeutics Unit, University of Ha’il, Ha’il 81442, Saudi Arabia
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
- Correspondence: (A.S.A.L.); (W.A.H.H.)
| | - Azza A. H. Rajab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Marwa H. Abdallah
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia
- Molecular Diagnostics and Personalized Therapeutics Unit, University of Ha’il, Ha’il 81442, Saudi Arabia
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Syed Mohd Danish Rizvi
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia
- Molecular Diagnostics and Personalized Therapeutics Unit, University of Ha’il, Ha’il 81442, Saudi Arabia
| | - Afrasim Moin
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81442, Saudi Arabia
- Molecular Diagnostics and Personalized Therapeutics Unit, University of Ha’il, Ha’il 81442, Saudi Arabia
| | - El-Sayed Khafagy
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Shams Tabrez
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Wael A. H. Hegazy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
- Pharmacy Program, Department of Pharmaceutical Sciences, Oman College of Health Sciences, Muscat 113, Oman
- Correspondence: (A.S.A.L.); (W.A.H.H.)
| |
Collapse
|
|
32
|
Mahgoub MA, Abbass AAG, Abaza AF, Shoukry MS. Probiotic lactic acid bacteria as a means of preventing in vitro urinary catheter colonization and biofilm formation. J Egypt Public Health Assoc 2023; 97:30. [PMID: 36593358 PMCID: PMC9807722 DOI: 10.1186/s42506-022-00124-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 10/29/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Catheter-associated urinary tract infections (CAUTIs) are the most common infections found in healthcare facilities. Urinary catheters predispose the development of CAUTIs by destroying natural barriers and providing a source for infection and biofilm formation (BF). This study aimed to evaluate probiotic lactic acid bacteria (LAB) as a means of preventing in vitro urinary catheter colonization and BF. METHODS Cross-sectional screening, followed by an experimental study, was conducted on 120 catheterized patients admitted to the urology department in a tertiary care hospital for 7 months. The isolated and identified uropathogens were tested for their antimicrobial susceptibility patterns by the disk diffusion method according to Clinical and Laboratory Standards Institute recommendations and examined for their ability to produce biofilms using a microtiter plate (MtP) assay. Five LAB (Lactobacillus acidophilus (L. acidophilus), Bifidobacterium bifidum (B. bifidum), L. paracasei, L. pentosus, and L. plantarum) were identified and examined for preventing in vitro colonization and BF of some isolated uropathogens on Foley urinary catheter surfaces. RESULTS Of the 120 samples collected, 32.5% were found to be associated with CAUTIs. Of isolated organisms, 74.4% were gram-negative bacilli, while gram-positive cocci represented 14%, and only 11.6% were of the Candida species. About two-thirds of isolated uropathogens were biofilm formers. All five probiotic strains had inhibitory effects on the growth of all the uropathogens tested but with varying intensities according to the duration of application after 2, 4, and 6 days. CONCLUSIONS The prevalence of CAUTIs was high, and the predominant bacterial isolates were gram-negative bacilli. Many of the studied uropathogens were biofilm formers. The bacterial isolates had a higher prevalence of resistance to commonly prescribed antimicrobial agents. Probiotics have the potential to prevent in vitro urinary catheter colonization and inhibit BF. Pre-coating urinary catheters with probiotics is recommended after ensuring the safety of probiotics' use in vivo by carrying out further large-scale studies.
Collapse
Affiliation(s)
- Mohamed Anwar Mahgoub
- grid.7155.60000 0001 2260 6941Department of Microbiology, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Aleya Abdel Gawad Abbass
- grid.7155.60000 0001 2260 6941Department of Microbiology, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Amani Farouk Abaza
- grid.7155.60000 0001 2260 6941Department of Microbiology, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Mohamed Shafik Shoukry
- grid.7155.60000 0001 2260 6941Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
33
|
Antibiotic Resistance and Biofilm Formation in Enterococcus spp. Isolated from Urinary Tract Infections. Pathogens 2022; 12:pathogens12010034. [PMID: 36678381 PMCID: PMC9863506 DOI: 10.3390/pathogens12010034] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/12/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Background: A urinary tract infection (UTI) resulting from multidrug-resistant (MDR) enterococci is a common disease with few therapeutic options. About 15% of urinary tract infections are caused by biofilm-producing Enterococcus spp. Therefore, the objective of this study was to identify the MDR enterococci associated with UTIs and assess their potential to produce biofilms. Methods: Thirty Enterococcus isolates were obtained from urine samples collected from UTI patients at King Abdulaziz Specialist Hospital in Taif, Saudi Arabia. The antimicrobial resistance profiles of the isolates were evaluated using disk diffusion techniques against 15 antimicrobial agents. Two techniques, Congo red agar (CRA) and a microtiter plate (MTP), were used to assess the potential of the isolates to produce biofilms. The enterococcal isolates were screened for biofilm-related genes, esp; ebpA; and ebpB, using the PCR method. Results: The molecular identification of the collected bacteria revealed the presence of 73.3% Enterococcus faecalis and 26.6% Enterococcus faecium. The antibiotic susceptibility test revealed that all the tested Enterococcus spp. were resistant to all antimicrobials except for linezolid and tigecycline. Additionally, by employing the CRA and MTP techniques, 76.6% and 100% of the Enterococcus isolates were able to generate biofilms, respectively. In terms of the association between the antibiotic resistance and biofilm’s formation, it was observed that isolates capable of creating strong biofilms were extremely resistant to most of the antibiotics tested. The obtained data showed that all the tested isolates had biofilm-encoding genes. Conclusions: Our research revealed that the biofilm-producing enterococci bacteria that causes urinary tract infections were resistant to antibiotics. Therefore, it is necessary to seek other pharmacological treatments if antibiotic medicine fails.
Collapse
|
|
34
|
Xu W, Ceylan Koydemir H. Non-invasive biomedical sensors for early detection and monitoring of bacterial biofilm growth at the point of care. LAB ON A CHIP 2022; 22:4758-4773. [PMID: 36398687 DOI: 10.1039/d2lc00776b] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Bacterial infections have long been a serious global health issue. Biofilm formation complicates matters even more. The biofilm's extracellular polymeric substances (EPSs) matrix protects bacteria from the host's immune responses, yielding strong adhesion and drug resistance as the biofilm matures. Early bacterial biofilm detection and bacterial biofilm growth monitoring are crucial to treating biofilm-associated infections. Current detection methods are highly sensitive but not portable, are time-consuming, and require expensive equipment and complex operating procedures, limiting their use at the point of care. Therefore, there is an urgent need to develop affordable, on-body, and non-invasive biomedical sensors to continuously monitor and detect early biofilm growth at the point of care through personalized telemedicine. Herein, recent advances in developing non-invasive biomedical sensors for early detection and monitoring bacterial biofilm growth are comprehensively reviewed. First, biofilm's life cycle and its impact on the human body, such as biofilm-associated disease and infected medical devices, are introduced together with the challenges of biofilm treatment. Then, the current methods used in clinical and laboratory settings for biofilm detection and their challenges are discussed. Next, the current state of non-invasive sensors for direct and indirect detection of bacterial biofilms are summarized and highlighted with the detection parameters and their design details. Finally, commercially available products, challenges of current devices, and the further trend in biofilm detection sensors are discussed.
Collapse
Affiliation(s)
- Weiming Xu
- Department of Biomedical Engineering, Texas A&M University, College Station, 77843, Texas, USA.
- Center for Remote Health Technologies and Systems, Texas A&M Engineering Experiment Station, College Station, 77843, TX, USA
| | - Hatice Ceylan Koydemir
- Department of Biomedical Engineering, Texas A&M University, College Station, 77843, Texas, USA.
- Center for Remote Health Technologies and Systems, Texas A&M Engineering Experiment Station, College Station, 77843, TX, USA
| |
Collapse
|
|
35
|
Gandra S, Takahashi S, Mitrani-Gold FS, Mulgirigama A, Ferrinho DA. A systematic scoping review of faropenem and other oral penems: treatment of Enterobacterales infections, development of resistance and cross-resistance to carbapenems. JAC Antimicrob Resist 2022; 4:dlac125. [PMID: 36570688 PMCID: PMC9777757 DOI: 10.1093/jacamr/dlac125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 11/16/2022] [Indexed: 12/24/2022] Open
Abstract
Background Antimicrobial resistance is an urgent global healthcare concern. Beyond carbapenems as broad-spectrum, often 'last resort' antibiotics, oral penem antibiotics currently are approved only in Japan and India, used for the treatment of indications including urinary tract infections (UTIs). Exploring oral penem use to better understand the impact of antibiotic resistance on public health would help inform the management of infectious diseases, including UTIs. Scoping Review Methodology This scoping review investigated the impact of faropenem and other oral penems on Enterobacterales infection treatment and evaluated evidence for faropenem resistance and cross-resistance to carbapenems. PubMed, Embase, J-STAGE and CiNii were searched for relevant English- or Japanese-language articles published between 1 January 1996 and 6 August 2021. Key Findings From 705 unique publications, 29 eligible articles were included (16 in vitro studies; 10 clinical trials; 2 in vitro and in vivo studies; and 1 retrospective medical chart review). Limited evidence described faropenem to treat infectious disease; only four randomized clinical trials were identified. Faropenem dosing regimens varied broadly within and between indications. One study indicated potential dependence of penem efficacy on underlying antibiotic resistance mechanisms, while several studies reported UTI persistence or recurrence after faropenem treatment. In vitro MIC data suggested some potential bacterial resistance to faropenem, while limited clinical data showed resistance emergence after faropenem treatment. Preliminary in vitro evidence suggested faropenem resistance might foster cross-resistance to carbapenems. Overall, very limited clinical evidence describes faropenem for treating infectious diseases. Preclinical and clinical research investment and dedicated community surveillance monitoring is crucial for understanding faropenem treatment patterns, resistance and potential cross-resistance to carbapenems.
Collapse
Affiliation(s)
- Sumanth Gandra
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Satoshi Takahashi
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
- Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | | | | |
Collapse
|
|
36
|
Tsuruta K, Butler A, Goic J. Effect of intermittent bladder flushing on recurrence rate in feline urethral obstruction: 72 cases. THE CANADIAN VETERINARY JOURNAL = LA REVUE VETERINAIRE CANADIENNE 2022; 63:1236-1241. [PMID: 36467381 PMCID: PMC9648483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
Objective To evaluate the effect of intermittent bladder flushing on recurrent urethral obstruction (rUO) at 7 d and 30 d after discharge and the risk of bacteriuria as a result of indwelling urethral catheterization. Animals There were 72 cats with suspected obstructive feline idiopathic cystitis admitted to the hospital. Procedures Cats were randomly assigned to either intermittent bladder flushing (n = 34) or no-flush (control) groups (n = 38). Bladder flushing was performed with 5 mL/kg of sterile 0.9% saline, q8h during indwelling urinary catheterization. Urine was tested for bacteriuria by a point-of-care test at the time of urinary catheterization and via cystocentesis following catheter removal before discharge. Risk of rUO by groups and its association with other variables were evaluated. Results The age (median: 3.0 years) in the flush group was younger (P = 0.01), and the length of hospitalization (> 24 hours) was longer (P < 0.01) than that of the control group. Overall rUO was 6.6% on Day 7 and 21.8% on Day 30 after discharge, but there was no significant difference between groups. A shorter duration of catheterization (< 24 hours) was associated with higher risk of rUO (odds ratio: 6.0). The incidence of catheter-related bacteriuria was 14.5% and was not significantly different between groups (13.8% and 15.2% in the flush and control, respectively). Conclusion and clinical relevance Intermittent bladder flushing during hospitalization appears safe but did not decrease the incidence of rUO. The incidence of bacteriuria following catheterization was not affected by intermittent bladder flushing.
Collapse
|
|
37
|
Sikarwar J, Singh J, Singh TP, Sharma P, Sharma S. The Mechanism of Action of Lactoferrin - Nucleoside Diphosphate Kinase Complex in Combating Biofilm Formation. Protein Pept Lett 2022; 29:839-850. [PMID: 35975859 DOI: 10.2174/0929866529666220816160517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/16/2022] [Accepted: 06/03/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND The ESKAPE group of pathogens which comprise of multidrug resistant bacteria, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are the cause of deadly nosocomial infections all over the world. While these pathogens have developed robust strategies to resist most antibiotics, their ability to form biofilms is one of their most combative properties. Hence there is an urgent need to discover new antibacterial agents which could prevent or destroy the biofilms made by these bacteria. Though it has been established that lactoferrin (LF), a potent iron binding antibacterial, antifungal, and antiviral protein displays anti-biofilm properties, its mechanisms of action, in addition to its iron chelation property, still remains unclear. OBJECTIVE The binding and inhibition studies of LF with the enzyme Nucleoside diphosphate Kinase (NDK) and its elastase cleaved truncated 12 kDa fragment (12-NDK). METHODS The characterization studies of NDK and 12-NDK using florescence spectroscopy, dynamic light scattering, size exclusion chromatography and ADP-glo Kinase Assay. Inhibition studies of LF-NDK using ADP-glo kinase assay, Surface Plasmon Resonance and Biofilm inhibition studies. RESULTS NDK and 12-NDK were cloned, expressed and purified from Acinetobacter baumannii and Pseudomonas aeruginosa. The characterization studies revealed NDK and 12-NDK from both species are stable and functional. The inhibition studies of LF-NDK revealed stable binding and inhibition of kinase activity by LF. CONCLUSION The binding and inhibition studies have shown that while LF binds with both the NDK and their truncated forms, it tends to have a higher binding affinity with the truncated 12 kDa fragments, resulting in their decreased kinase activity. This study essentially gives a new direction to the field of inhibition of biofilm formation, as it proves that LF has a novel mechanism of action in other than iron sequestration.
Collapse
Affiliation(s)
- Juhi Sikarwar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi - 110029, India
| | - Jiya Singh
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi - 110029, India
| | - Tej P Singh
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi - 110029, India
| | - Pradeep Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi - 110029, India
| | - Sujata Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi - 110029, India
| |
Collapse
|
|
38
|
Krukiewicz K, Kazek-Kęsik A, Brzychczy-Włoch M, Łos MJ, Ateba CN, Mehrbod P, Ghavami S, Shyntum DY. Recent Advances in the Control of Clinically Important Biofilms. Int J Mol Sci 2022; 23:9526. [PMID: 36076921 PMCID: PMC9455909 DOI: 10.3390/ijms23179526] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 08/17/2022] [Accepted: 08/20/2022] [Indexed: 11/16/2022] Open
Abstract
Biofilms are complex structures formed by bacteria, fungi, or even viruses on biotic and abiotic surfaces, and they can be found in almost any part of the human body. The prevalence of biofilm-associated diseases has increased in recent years, mainly because of the frequent use of indwelling medical devices that create opportunities for clinically important bacteria and fungi to form biofilms either on the device or on the neighboring tissues. As a result of their resistance to antibiotics and host immunity factors, biofilms have been associated with the development or persistence of several clinically important diseases. The inability to completely eradicate biofilms drastically increases the burden of disease on both the patient and the healthcare system. Therefore, it is crucial to develop innovative ways to tackle the growth and development of biofilms. This review focuses on dental- and implant-associated biofilm infections, their prevalence in humans, and potential therapeutic intervention strategies, including the recent advances in pharmacology and biomedical engineering. It lists current strategies used to control the formation of clinically important biofilms, including novel antibiotics and their carriers, antiseptics and disinfectants, small molecule anti-biofilm agents, surface treatment strategies, and nanostructure functionalization, as well as multifunctional coatings particularly suitable for providing antibacterial effects to the surface of implants, to treat either dental- or implant-related bacterial infections.
Collapse
Affiliation(s)
- Katarzyna Krukiewicz
- Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, M. Strzody 9, 44-100 Gliwice, Poland
- Centre for Organic and Nanohybrid Electronics, Silesian University of Technology, Konarskiego 22B, 44-100 Gliwice, Poland
| | - Alicja Kazek-Kęsik
- Department of Inorganic Chemistry, Analytical Chemistry and Electrochemistry, Silesian University of Technology, 44-100 Gliwice, Poland
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8 Street, 44-100 Gliwice, Poland
| | - Monika Brzychczy-Włoch
- Department of Molecular Medical Microbiology, Chair of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Czysta 18 Street, 31-121 Krakow, Poland
| | - Marek J. Łos
- Department of Pathology, Pomeranian Medical University, 71-344 Szczecin, Poland
| | - Collins Njie Ateba
- Food Security and Safety Niche Area, North West University, Private Bag X2046, Mahikeng 2735, South Africa
| | - Parvaneh Mehrbod
- Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Saeid Ghavami
- Faculty of Medicine in Zabrze, University of Technology in Katowice, Academia of Silesia, 41-800 Zabrze, Poland
- Research Institute of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB R3E 3P5, Canada
- Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P5, Canada
- Department of Human Anatomy and Cell Science, University of Manitoba College of Medicine, Winnipeg, MB R3E 3P5, Canada
| | - Divine Yufetar Shyntum
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8 Street, 44-100 Gliwice, Poland
| |
Collapse
|
|
39
|
Ognenovska S, Mukerjee C, Sanderson-Smith M, Moore KH, Mansfield KJ. Virulence Mechanisms of Common Uropathogens and Their Intracellular Localisation within Urothelial Cells. Pathogens 2022; 11:pathogens11080926. [PMID: 36015046 PMCID: PMC9415470 DOI: 10.3390/pathogens11080926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/12/2022] [Accepted: 08/15/2022] [Indexed: 11/29/2022] Open
Abstract
A recurrent urinary tract infection (UTI) is a common debilitating condition whereby uropathogens are able to survive within the urinary tract. In this study, we aimed to determine if the common uropathogens Escherichia coli, Enterococcus faecalis, and Group B Streptococcus possessed virulence mechanisms that enable the invasion of urothelial cells. Urothelial cells were isolated from women with detrusor overactivity and recurrent UTIs; the intracellular localisation of the uropathogens was determined by confocal microscopy. Uropathogens were also isolated from women with acute UTIs and their intracellular localisation and virulence mechanisms were examined (yeast agglutination, biofilm formation, and haemolysis). Fluorescent staining and imaging of urothelial cells isolated from women with refractory detrusor overactivity and recurrent UTIs demonstrated that all three uropathogens were capable of intracellular colonisation. Similarly, the bacterial isolates from women with acute UTIs were also seen to intracellularly localise using an in vitro model. All Enterococcus and Streptococcus isolates possessed a haemolytic capacity and displayed a strong biofilm formation whilst yeast cell agglutination was unique to Escherichia coli. The expression of virulence mechanisms by these uropathogenic species was observed to correlate with successful urothelial cell invasion. Invasion into the bladder urothelium was seen to be a common characteristic of uropathogens, suggesting that bacterial reservoirs within the bladder contribute to the incidence of recurrent UTIs.
Collapse
Affiliation(s)
- Samantha Ognenovska
- Detrusor Muscle Laboratory, Department of Urogynaecology, University of New South Wales, St. George Hospital, Sydney, NSW 2217, Australia
| | - Chinmoy Mukerjee
- Department of Microbiology, St. George Hospital, Sydney, NSW 2217, Australia
| | - Martina Sanderson-Smith
- Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia
- Molecular Horizons, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Kate H. Moore
- Detrusor Muscle Laboratory, Department of Urogynaecology, University of New South Wales, St. George Hospital, Sydney, NSW 2217, Australia
| | - Kylie J. Mansfield
- Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia
- Graduate School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia
- Correspondence:
| |
Collapse
|
|
40
|
Acquaviva A, Cristina Di Simone S, Canini A, Braglia R, Di Marco G, Campana C, Angelini P, Angeles Flores G, Venanzoni R, Loreta Libero M, Tirillini B, Zengin G, Chiavaroli A, Recinella L, Leone S, Nilofar, Brunetti L, Orlando G, Menghini L, Ferrante C. Phytochemical and biological investigations on the pollen from industrial hemp male inflorescences. Food Res Int 2022; 161:111883. [DOI: 10.1016/j.foodres.2022.111883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/22/2022] [Accepted: 08/25/2022] [Indexed: 11/04/2022]
|
|
41
|
Tan CAZ, Lam LN, Biukovic G, Soh EYC, Toh XW, Lemos JA, Kline KA. Enterococcus faecalis Antagonizes Pseudomonas aeruginosa Growth in Mixed-Species Interactions. J Bacteriol 2022; 204:e0061521. [PMID: 35758750 PMCID: PMC9295543 DOI: 10.1128/jb.00615-21] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 06/05/2022] [Indexed: 12/30/2022] Open
Abstract
Enterococcus faecalis is often coisolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their coprevalence, the polymicrobial interactions of these two species in biofilms and under iron-restricted conditions remain unexplored. Here, we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to l-lactate production during fermentative growth. We find that an E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced under iron-restricted conditions, resulting in increased lactic acid exported and, consequently, a reduction in local environmental pH. Together, our results suggest that E. faecalis synergistically inhibits P. aeruginosa growth by decreasing environmental pH and l-lactate-mediated iron chelation. Overall, this study emphasizes the importance of the microenvironment in polymicrobial interactions and how manipulating the microenvironment can impact the growth trajectory of bacterial communities. IMPORTANCE Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored under iron-restricted conditions. Here, we explore the polymicrobial interactions between commonly coisolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron and also lowers the environmental pH to antagonize P. aeruginosa growth under iron-restricted conditions. Our findings provide insights into polymicrobial interactions between bacteria and how manipulating the microenvironment can be taken advantage of to better control infections.
Collapse
Affiliation(s)
- Casandra Ai Zhu Tan
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
| | - Ling Ning Lam
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USA
| | - Goran Biukovic
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
| | - Eliza Ye-Chen Soh
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
| | - Xiao Wei Toh
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
| | - José A. Lemos
- Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USA
| | - Kimberly A. Kline
- Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore
- School of Biological Sciences, Nanyang Technological University, Singapore
| |
Collapse
|
|
42
|
Kanlaya R, Thongboonkerd V. Persistent Escherichia coli infection in renal tubular cells enhances calcium oxalate crystal-cell adhesion by inducing ezrin translocation to apical membranes via Rho/ROCK pathway. Cell Mol Life Sci 2022; 79:381. [PMID: 35751006 PMCID: PMC11072855 DOI: 10.1007/s00018-022-04414-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/28/2022] [Accepted: 06/06/2022] [Indexed: 01/18/2023]
Abstract
Recent evidence has suggested that recurrent urinary tract infection (UTI) can cause not only infection stones but also metabolic stones (e.g., those containing calcium oxalate monohydrate or COM). However, precise mechanisms underlying UTI-induced metabolic stones remained unknown. In this study, Escherichia coli, the most common bacterium found in recurrent UTI was used to establish the in vitro model for persistent infection of renal epithelial cells. The promoting effects of persistent E. coli infection on kidney stone formation were validated by COM crystal-cell adhesion assay, followed by immunofluorescence study for changes in surface expression of the known COM crystal receptors. Among the five receptors examined, only ezrin had significantly increased level on the surface of persistently infected cells without change in its total level. Such translocation of ezrin to apical membranes was confirmed by Western blotting of apical membrane and cytosolic fractions and confocal microscopic examination. Additionally, persistent infection increased phosphorylation (Thr567) of ezrin. However, all of these changes induced by persistent E. coli infection were significantly inhibited by small-interfering RNA (siRNA) specific for ezrin or a Rho-associated kinase (ROCK)-specific inhibitor (Y-27632). In summary, this study provides a piece of evidence demonstrating that persistent infection by E. coli, one of the non-urease-producing bacteria, may contribute to COM metabolic stone formation by translocation of ezrin to apical membranes, thereby promoting COM crystal-cell adhesion. Such ezrin translocation was mediated via Rho/ROCK signaling pathway. These findings may, at least in part, explain the pathogenic mechanisms underlying recurrent UTI-induced metabolic kidney stone disease.
Collapse
Affiliation(s)
- Rattiyaporn Kanlaya
- Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, 6th Floor - SiMR Building, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Visith Thongboonkerd
- Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, 6th Floor - SiMR Building, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
| |
Collapse
|
|
43
|
Ndukwe ARN, Wiedbrauk S, Boase NRB, Fairfull‐Smith KE. Strategies to Improve the Potency of Oxazolidinones towards Bacterial Biofilms. Chem Asian J 2022; 17:e202200201. [PMID: 35352479 PMCID: PMC9321984 DOI: 10.1002/asia.202200201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/28/2022] [Indexed: 11/29/2022]
Abstract
Biofilms are part of the natural lifecycle of bacteria and are known to cause chronic infections that are difficult to treat. Most antibiotics are developed and tested against bacteria in the planktonic state and are ineffective against bacterial biofilms. The oxazolidinones, including the last resort drug linezolid, are one of the main classes of synthetic antibiotics progressed to clinical use in the last 50 years. They have a unique mechanism of action and only develop low levels of resistance in the clinical setting. With the aim of providing insight into strategies to design more potent antibiotic compounds with activity against bacterial biofilms, we review the biofilm activity of clinically approved oxazolidinones and report on structural modifications to oxazolidinones and their delivery systems which lead to enhanced anti-biofilm activity.
Collapse
Affiliation(s)
- Audrey R. N. Ndukwe
- School of Chemistry and Physics, Faculty of ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
- Centre for Materials ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
| | - Sandra Wiedbrauk
- School of Chemistry and Physics, Faculty of ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
- Centre for Materials ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
| | - Nathan R. B. Boase
- School of Chemistry and Physics, Faculty of ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
- Centre for Materials ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
| | - Kathryn E. Fairfull‐Smith
- School of Chemistry and Physics, Faculty of ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
- Centre for Materials ScienceQueensland University of TechnologyBrisbaneQueensland4001Australia
| |
Collapse
|
|
44
|
Qian W, Li X, Yang M, Liu C, Kong Y, Li Y, Wang T, Zhang Q. Relationship Between Antibiotic Resistance, Biofilm Formation, and Biofilm-Specific Resistance in Escherichia coli Isolates from Ningbo, China. Infect Drug Resist 2022; 15:2865-2878. [PMID: 35686192 PMCID: PMC9172925 DOI: 10.2147/idr.s363652] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 05/17/2022] [Indexed: 01/09/2023] Open
Abstract
Purpose Methods Results Conclusion
Collapse
Affiliation(s)
- Weidong Qian
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, People’s Republic of China
| | - Xinchen Li
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, People’s Republic of China
| | - Min Yang
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, People’s Republic of China
| | - Chanchan Liu
- Xi’an Medical College, Xi’an, 710309, People’s Republic of China
| | - Yi Kong
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, the General Hospital of the People’s Liberation Army, Beijing, 100048, People’s Republic of China
| | - Yongdong Li
- Ningbo Municipal Center for Disease Control and Prevention, Ningbo, 315010, People’s Republic of China
| | - Ting Wang
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, People’s Republic of China
- Correspondence: Ting Wang; Qian Zhang, Tel +10 29-86168583, Email ;
| | - Qian Zhang
- Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518004, People’s Republic of China
| |
Collapse
|
|
45
|
Marquez-Algaba E, Burgos J, Almirante B. Pharmacotherapeutic interventions for the treatment of bacterial prostatitis. Expert Opin Pharmacother 2022; 23:1091-1101. [PMID: 35574695 DOI: 10.1080/14656566.2022.2077101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Bacterial prostatitis, acute or chronic, is one of the most prevalent urogenital infections in men. Its diagnosis requires the application of a careful methodology. Gram-negative bacilli are the most frequent causative agents, and in recent years, an increase in the frequency of multiresistant bacteria has been detected. The choice of the optimal antimicrobial treatment requires the selection of drugs with proven in vitro activity associated with good penetration into the prostatic tissue, especially in chronic forms of infection. AREAS COVERED The aim of this article is to summarize the current evidence regarding the pathogenesis, etiology, empirical and definitive antimicrobial therapy, and new pharmacotherapeutic interventions to improve the prognosis of bacterial acute or chronic prostatitis. EXPERT OPINION Bacterial prostatitis requires the application of an accurate diagnostic protocol to identify the causative agent and establish the optimal antimicrobial treatment. The structural and biochemical characteristics of prostatic tissue result in poor penetration of antimicrobials; therefore, in the choice of treatment, it is essential to select agents with proven antimicrobial activity and pharmacokinetic characteristics that ensure good and sustained concentrations in this area. Patients with chronic forms of infection require prolonged treatment, and relapses of the infectious process are frequent.
Collapse
Affiliation(s)
- Ester Marquez-Algaba
- Department of Infectious Diseases, Vall d'Hebron Hospital Universitari, Barcelona, Spain.,Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Joaquin Burgos
- Department of Infectious Diseases, Vall d'Hebron Hospital Universitari, Barcelona, Spain.,Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.,Red Española de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Madrid, Spain
| | - Benito Almirante
- Department of Infectious Diseases, Vall d'Hebron Hospital Universitari, Barcelona, Spain.,Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain.,Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
46
|
Crude metabolites from endophytic fungi inhabiting Cameroonian Annona muricata inhibit the causative agents of urinary tract infections. PLoS One 2022; 17:e0267246. [PMID: 35544583 PMCID: PMC9094522 DOI: 10.1371/journal.pone.0267246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/06/2022] [Indexed: 12/20/2022] Open
Abstract
Urinary tract infections (UTIs) are common bacterial infections. The global emergence of multidrug-resistant uropathogens in the last decade underlines the need to search for new antibiotics with novel mechanisms of action. In this regard, exploring endophytic fungi inhabiting medicinal plants used locally against urinary tract infections could be a promising strategy for novel drug discovery. This study investigates crude metabolites from endophytic fungi isolated from Annona muricata as potential sources of antibiotic drugs to fight against uropathogens and reduce related oxidative stress. Crude ethyl acetate extracts from 41 different endophytic fungi were screened against three bacterial strains using the broth microdilution method, and fungi producing active crude extracts were identified using ITS1-5.8S rRNA-ITS2 nucleotide sequences. The antibacterial modes of action of the five most active extracts were evaluated using Staphylococcus aureus ATCC 43300 and Klebsiella oxytoca strains. The DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 41 crude extracts tested, 17 were active with minimum inhibitory concentrations (MICs) ranging from 3.125 μg/mL to 100 μg/mL and were not cytotoxic against Vero cell lines with a cytotoxic concentration 50 (CC50) >100 μg/mL. The more potent extracts (from Fusarium waltergamsii AMtw3, Aspergillus sp. AMtf15, Penicillium citrinum AMf6, Curvularia sp. AMf4, and Talaromyces annesophieae AMsb23) significantly inhibited bacterial catalase activity, lysed bacterial cells, increased outer membrane permeability, and inhibited biofilm formation, and the time-kill kinetic assay revealed concentration-dependent bactericidal activity. All seventeen extracts showed weak ferric iron-reducing power (1.06 to 12.37 μg equivalent NH2OH/g of extract). In comparison, seven extracts exhibited DPPH free radical scavenging activity, with RSA50 ranging from 146.05 to 799.75 μg/mL. The molecular identification of the seventeen active fungi revealed that they belong to six distinct genera, including Aspergillus, Curvularia, Fusarium, Meyerozyma, Penicillium, and Talaromyces. This investigation demonstrated that fungal endophytes from Cameroonian Annona muricata, a medicinal plant used locally to treat bacterial infections, might contain potent antibacterial metabolites with multiple modes of action. The antibacterial-guided fractionation of these active extracts is currently ongoing to purify and characterise potential antibacterial active ingredients.
Collapse
|
|
47
|
Cui S, Qiao J, Xiong MP. Antibacterial and Biofilm-Eradicating Activities of pH-Responsive Vesicles against Pseudomonas aeruginosa. Mol Pharm 2022; 19:2406-2417. [PMID: 35507414 DOI: 10.1021/acs.molpharmaceut.2c00165] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The formation of biofilms by a microcolony of bacteria is a significant burden on the healthcare industry due to difficulty eradicating it. In this study, pH-responsive vesicles capable of releasing apramycin (APR), a model aminoglycoside antibiotic, in response to the low pH typical of establishedPseudomonas aeruginosa biofilms resulted in improved eradication of existing biofilms in comparison to the free drug. The amphiphilic polymeric vesicle (PV) comprised of block polymer poly (ethylene glycol)-block-poly 2-(dimethylamino) ethyl methacrylate (mPEG-b-pDEAEMA) averaged 128 nm. The drug encapsulation content of APR in PV/APR was confirmed to be 28.2%, and the drug encapsulation efficiency was confirmed to be 51.2%. At pH 5.5, PV/APR released >90% APR after 24 h compared to <20% at pH 7.4. At pH 5.5, protonation of the pDEAEMA block results in a zeta potential of +23 mV compared to a neutral zeta potential of +2.2 mV at pH 7.4. Confocal microscopy, flow cytometry, and scanning electron microscopy reveal that the positively charged vesicles can compromise the integrity of the planktonic bacterial membrane in a pH-dependent manner. In addition, PV/APR is able to diffuse into mature biofilms to release APR in the acidic milieu of biofilm bacteria, and PV/APR was more efficient at eliminating preexisting biofilms compared to free APR at 128 and 256 μg/mL. This study reveals that dynamic charge density in response to pH can lead to differential levels of interactions with the biofilm and bacterial membrane. This effectively results in enhanced antibacterial and antibiofilm properties against both planktonic and difficult-to-treat biofilm bacteria at concentrations significantly lower than those of the free drug. Overall, this pH-responsive vesicle could be especially promising for treating biofilm-associated infectious diseases.
Collapse
Affiliation(s)
- Shuolin Cui
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602-2352, United States
| | - Jing Qiao
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602-2352, United States.,Institute of Advanced Materials, School of Chemistry and Chemical Engineering, and, Jiangsu Province Hi-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 211189, China
| | - May P Xiong
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602-2352, United States
| |
Collapse
|
|
48
|
Müller M, Sägesser N, Keller PM, Arampatzis S, Steffens B, Ehrhard S, Leichtle AB. Urine Flow Cytometry Parameter Cannot Safely Predict Contamination of Urine—A Cohort Study of a Swiss Emergency Department Using Machine Learning Techniques. Diagnostics (Basel) 2022; 12:diagnostics12041008. [PMID: 35454055 PMCID: PMC9025120 DOI: 10.3390/diagnostics12041008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/10/2022] [Accepted: 04/13/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Urine flow cytometry (UFC) analyses urine samples and determines parameter counts. We aimed to predict different types of urine culture growth, including mixed growth indicating urine culture contamination. Methods: A retrospective cohort study (07/2017–09/2020) was performed on pairs of urine samples and urine cultures obtained from adult emergency department patients. The dataset was split into a training (75%) and validation set (25%). Statistical analysis was performed using a machine learning approach with extreme gradient boosting to predict urine culture growth types (i.e., negative, positive, and mixed) using UFC parameters obtained by UF-4000, sex, and age. Results: In total, 3835 urine samples were included. Detection of squamous epithelial cells, bacteria, and leukocytes by UFC were associated with the different types of culture growth. We achieved a prediction accuracy of 80% in the three-class approach. Of the n = 126 mixed cultures in the validation set, 11.1% were correctly predicted; positive and negative cultures were correctly predicted in 74.0% and 96.3%. Conclusions: Significant bacterial growth can be safely ruled out using UFC parameters. However, positive urine culture growth (rule in) or even mixed culture growth (suggesting contamination) cannot be adequately predicted using UFC parameters alone. Squamous epithelial cells are associated with mixed culture growth.
Collapse
Affiliation(s)
- Martin Müller
- Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (S.A.); (S.E.)
- Correspondence: ; Tel.: +41-(0)-31-632-2111
| | - Nadine Sägesser
- University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (N.S.); (A.B.L.)
| | - Peter M. Keller
- Institute for Infectious Diseases, University of Bern, 3010 Bern, Switzerland;
| | - Spyridon Arampatzis
- Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (S.A.); (S.E.)
| | - Benedict Steffens
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany;
| | - Simone Ehrhard
- Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (S.A.); (S.E.)
| | - Alexander B. Leichtle
- University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (N.S.); (A.B.L.)
- Center for Artificial Intelligence in Medicine (CAIM), University of Bern, 3010 Bern, Switzerland
| |
Collapse
|
|
49
|
Chakrabarty S, Mishra MP, Bhattacharyay D. Targeting Microbial Bio-film: an Update on MDR Gram-Negative Bio-film Producers Causing Catheter-Associated Urinary Tract Infections. Appl Biochem Biotechnol 2022; 194:2796-2830. [PMID: 35247153 DOI: 10.1007/s12010-021-03711-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/08/2021] [Indexed: 11/26/2022]
Abstract
In every age group, urinary tract infection (UTI) is found as a major recurrence infectious disorder. Bio-films produced by bacteria perform a vital role in causing infection in the tract of the urinary system, leading to recurrences and relapses. The purpose of this review is to present the role and mechanism of bio-film producing MDR Gram-negative bacteria causing UTI, their significance, additionally the challenges for remedy and prevention of catheter-associated UTI. This work appreciates a new understanding of bio-film producers which are having multi-drug resistance capability and focuses on the effect and control of bio-film producing uropathogenic bacteria related to catheterization. We have tried to analyze approaches to target bio-film and reported phytochemicals with anti-bio-film activity also updated on anti-bio-film therapy.
Collapse
Affiliation(s)
- Susmita Chakrabarty
- School of Paramedics and Allied Health Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India
| | - Monali P Mishra
- School of Paramedics and Allied Health Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India.
| | - Dipankar Bhattacharyay
- School of Applied Sciences, Centurion University of Technology and Management, Sitapur, Odisha, India
| |
Collapse
|
|
50
|
Tuon FF, Dantas LR, Suss PH, Tasca Ribeiro VS. Pathogenesis of the Pseudomonas aeruginosa Biofilm: A Review. Pathogens 2022; 11:pathogens11030300. [PMID: 35335624 PMCID: PMC8950561 DOI: 10.3390/pathogens11030300] [Citation(s) in RCA: 154] [Impact Index Per Article: 51.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/08/2022] [Accepted: 02/24/2022] [Indexed: 01/21/2023] Open
Abstract
Pseudomonas aeruginosa is associated with several human infections, mainly related to healthcare services. In the hospital, it is associated with resistance to several antibiotics, which poses a great challenge to therapy. However, one of the biggest challenges in treating P. aeruginosa infections is that related to biofilms. The complex structure of the P. aeruginosa biofilm contributes an additional factor to the pathogenicity of this microorganism, leading to therapeutic failure, in addition to escape from the immune system, and generating chronic infections that are difficult to eradicate. In this review, we address several molecular aspects of the pathogenicity of P. aeruginosa biofilms.
Collapse
|