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Kalaba MH, El-Sherbiny GM, Ewais EA, Darwesh OM, Moghannem SA. Green synthesis of zinc oxide nanoparticles (ZnO-NPs) by Streptomyces baarnensis and its active metabolite (Ka): a promising combination against multidrug-resistant ESKAPE pathogens and cytotoxicity. BMC Microbiol 2024; 24:254. [PMID: 38982372 PMCID: PMC11232237 DOI: 10.1186/s12866-024-03392-4] [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: 04/14/2024] [Accepted: 06/20/2024] [Indexed: 07/11/2024] Open
Abstract
Various eco-friendly techniques are being researched for synthesizing ZnO-NPs, known for their bioactivity. This study aimed at biosynthesizing ZnO-NPs using Streptomyces baarnensis MH-133, characterizing their physicochemical properties, investigating antibacterial activity, and enhancement of their efficacy by combining them with a water-insoluble active compound (Ka) in a nanoemulsion form. Ka is a pure compound of 9-Ethyl-1,4,6,9,10-pentahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione obtained previously from our strain of Streptomyces baarnensis MH-133. Biosynthesized ZnO-NPs employing Streptomyces baarnensis MH-133 filtrate and zinc sulfate (ZnSO4.7H2O) as a precursor were purified and characterized by physicochemical investigation. High-resolution-transmission electron microscopy (HR-TEM) verified the effective biosynthesis of ZnO-NPs (size < 12 nm), whereas dynamic light scattering (DLS) analysis showed an average size of 17.5 nm. X-ray diffraction (XRD) exhibited characteristic diffraction patterns that confirmed crystalline structure. ZnO-NPs efficiently inhibited both Gram-positive and Gram-negative bacteria (MICs: 31.25-125 µg/ml). The pure compound (Ka) was combined with ZnO-NPs to improve effectiveness and reduce dose using checkerboard microdilution. Niteen treatments of Ka and ZnO-NPs combinations obtained by checkerboard matrix inhibited Klebsiella pneumonia. Eleven combinations had fractional inhibitory concentration index (FICi) between 1.03 and 2, meaning indifferent, another five combinations resulted from additive FICi (0.625-1) and only one combination with FICi of 0.5, indicating synergy. In the case of methicillin-resistant S. aureus (MRSA), Ka-ZnO-NPs combinations yielded 23 treatments with varying degrees of interaction. The results showed eleven treatments with indifferent interaction, eight additive interactions, and two synergies with FICi of 0.5 and 0.375. The combinations that exhibited synergy action were transformed into a nanoemulsion form to improve their solubility and bioavailability. The HR-TEM analysis of the nanoemulsion revealed spherical oil particles with a granulated core smaller than 200 nm and no signs of aggregation. Effective dispersion was confirmed by DLS analysis which indicated that Ka-ZnO-NPs nanoemulsion droplets have an average size of 53.1 nm and a polydispersity index (PI) of 0.523. The killing kinetic assay assessed the viability of methicillin-resistant Staphylococcus aureus (MRSA) and K. pneumonia post-treatment with Ka-ZnO-NPs combinations either in non-formulated or nanoemulsion form. Results showed Ka-ZnO-NPs combinations show concentration and time-dependent manner, with higher efficacy in nanoemulsion form. The findings indicated that Ka-ZnO-NPs without formulation at MIC values killed K. pneumonia after 24 h but not MRSA. Our nanoemulsion loaded with the previously mentioned combinations at MIC value showed bactericidal effect at MIC concentration of Ka-ZnO-NPs combination after 12 and 18 h of incubation against MRSA and K. pneumonia, respectively, compared to free combinations. At half MIC value, nanoemulsion increased the activity of the combinations to cause a bacteriostatic effect on MRSA and K. pneumonia after 24 h of incubation. The free combination showed a bacteriostatic impact for 6 h before the bacteria regrew to increase log10 colony forming unit (CFU)/ml over the initial level. Similarly, the cytotoxicity study revealed that the combination in nanoemulsion form decreased the cytotoxicity against kidney epithelial cells of the African green monkey (VERO) cell line. The IC50 for Ka-ZnO-NPs non-formulated treatment was 8.17/1.69 (µg/µg)/ml, but in nano-emulsion, it was 22.94 + 4.77 (µg/µg)/mL. In conclusion, efficient Ka-ZnO-NPs nanoemulsion may be a promising solution for the fighting of ESKAPE pathogenic bacteria according to antibacterial activity and low toxicity.
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Affiliation(s)
- Mohamed H Kalaba
- Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, 11884, Egypt
| | - Gamal M El-Sherbiny
- Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, 11884, Egypt.
| | - Emad A Ewais
- Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, 11884, Egypt
| | - Osama M Darwesh
- Agricultural Microbiology Department, National Research Centre, Dokki, Cairo, Egypt
| | - Saad A Moghannem
- Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, 11884, Egypt
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He Y, Luo L, Liu L. Photodynamic therapy for treatment of burns: A system review and meta-analysis of animal study. Photodiagnosis Photodyn Ther 2024; 45:103905. [PMID: 38013017 DOI: 10.1016/j.pdpdt.2023.103905] [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: 08/17/2023] [Revised: 11/18/2023] [Accepted: 11/20/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND AND AIM Burns are common in both everyday life and war. Shock, infection, and organ dysfunction are major complications, among which infection is the most common and has the highest mortality rate. The aim of this study was to evaluate the effect of photodynamic therapy(PDT) on animals suffering from burns. METHODS Through searching Embase, PubMed, Web of Science, and the Cochrane Library, only controlled trials were collected to study the effects of PDT on animals with burns. The included studies were evaluated for methodological quality by the MINORS (Methodological Index for Non-Randomized Studies) assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS 16 articles were collected between the earliest available date and August 2022. The results of the meta-analysis showed that PDT effectively reduces TNF-α and IL-6 levels in wounds, and increases bFGF and VEGF levels, PDT can also reduce bacterial colonization at the injury site, accelerate the healing of burn wounds, and improve the survival rate. CONCLUSION PDT has been shown to have positive effects as a treatment for animals suffering from burns. It affects the levels of cytokines, reduces bacterial counts in wounds, promotes wound healing, and improves animal survival rates.
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Affiliation(s)
- Yue He
- Chengdu Second People's Hospital, Chengdu, Sichuan, 610021, China.
| | - Lun Luo
- Chengdu Second People's Hospital, Chengdu, Sichuan, 610021, China.
| | - Luoji Liu
- Chengdu Second People's Hospital, Chengdu, Sichuan, 610021, China
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Cui Z, Li Y, Qin Y, Li J, Shi L, Wan M, Hu M, Chen Y, Ji Y, Hou Y, Ye F, Liu C. Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M 1/M 2 macrophage polarization. J Control Release 2024; 366:297-311. [PMID: 38161034 DOI: 10.1016/j.jconrel.2023.12.046] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 11/27/2023] [Accepted: 12/26/2023] [Indexed: 01/03/2024]
Abstract
Multidrug-resistant (MDR) Acinetobacter baumannii infections pose a significant challenge in burn wound management, necessitating the development of innovative therapeutic strategies. In this work, we introduced a novel polymyxin B (PMB)-targeted liposomal photosensitizer, HMME@Lipo-PMB, for precise and potent antimicrobial photodynamic therapy (aPDT) against burn infections induced by MDR A. baumanni. HMME@Lipo-PMB-mediated aPDT exhibited enhanced antibacterial efficacy by specifically targeting and disrupting bacterial cell membranes, and generating increased intracellular ROS. Remarkably, even at low concentrations, this targeted approach significantly reduced bacterial viability in vitro and completely eradicated burn infections induced by MDR A. baumannii in vivo. Additionally, HMME@Lipo-PMB-mediated aPDT facilitated burn infection wound healing by modulating M1/M2 macrophage polarization. It also effectively promoted acute inflammation in the early stage, while attenuated chronic inflammation in the later stage of wound healing. This dynamic modulation promoted the formation of granulation tissue, angiogenesis, and collagen regeneration. These findings demonstrate the tremendous potential of HMME@Lipo-PMB-mediated aPDT as a promising alternative for the treatment of burn infections caused by MDR A. baumannii.
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Affiliation(s)
- Zixin Cui
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China; Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Yiyang Li
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China; Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Yannan Qin
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China
| | - Jianzhou Li
- Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Lei Shi
- Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Meijuan Wan
- Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Min Hu
- Department of Chemistry, School of Chemistry, Xi'an Jiaotong University, 28 Xianning West Road, Xi'an 710049, PR China
| | - Yunru Chen
- Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China
| | - Yanhong Ji
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China
| | - Yuzhu Hou
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China
| | - Feng Ye
- Department of Infection, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, PR China.
| | - Chengcheng Liu
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, PR China.
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Babaeekhou L, Ghane M, Mohammad Rafiee M. Photodynamic Therapy and Its Synergism with Melittin Against Drug-Resistant Acinetobacter baumannii Isolates with High Biofilm Formation Ability. Curr Microbiol 2023; 80:324. [PMID: 37596435 DOI: 10.1007/s00284-023-03356-3] [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: 09/01/2021] [Accepted: 05/29/2023] [Indexed: 08/20/2023]
Abstract
Drug-resistant biofilm producer A. baumannii isolates are a global concern that warns researchers about the development of new treatments. This study was designed to analyze the effect of photodynamic therapy (PDT) as monotherapy and associated with melittin on multidrug-resistant A. baumannii isolates. Sub-lethal doses of photosensitizer, LED, and PDT were determined. The PDT effect on the biofilm and expression of biofilm-associated genes was evaluated by scanning electron microscopy and quantitative real-time PCR (qRT-PCR) methods, respectively. The synergistic effect of PDT and melittin on the survival of MDR/XDR strong biofilm producer isolates was evaluated by checkerboard assay. Survival rates were significantly decreased at the lowest concentration of 12.5-50 μg/ml in 4 min at an energy density of 93.75 J/cm2 (P < 0.05). The optimized PDT method had a bactericidal effect against all tested groups, and the mean expression levels of csu, abaI, bap, and ompA genes in the strong biofilm producers were decreased significantly compared to the control group. The combined effect of LED and melittin successfully reduced the MDR/XDR A. baumannii strong biofilm producers' growth from 3.1 logs. MB-mediated aPDT and combined treatment of PDT with melittin, which has been investigated for the first time in this study, can be an efficient strategy against MDR/XDR A. baumannii isolates with strong biofilm production capacity.
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Affiliation(s)
- Laleh Babaeekhou
- Department of Biology, Islamshahr Branch, Islamic Azad University, Sayyad Shirazi St., P.O. Box: 33135/369, Eslamshahr, Iran.
- Department of Biology, Islamshahr Branch, Islamic Azad University, Eslamshahr, Iran.
| | - Maryam Ghane
- Department of Biology, Islamshahr Branch, Islamic Azad University, Eslamshahr, Iran
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Dolma KG, Khati R, Paul AK, Rahmatullah M, de Lourdes Pereira M, Wilairatana P, Khandelwal B, Gupta C, Gautam D, Gupta M, Goyal RK, Wiart C, Nissapatorn V. Virulence Characteristics and Emerging Therapies for Biofilm-Forming Acinetobacter baumannii: A Review. BIOLOGY 2022; 11:biology11091343. [PMID: 36138822 PMCID: PMC9495682 DOI: 10.3390/biology11091343] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/04/2022] [Accepted: 09/08/2022] [Indexed: 11/20/2022]
Abstract
Simple Summary Acinetobacter baumannii (A. baumannii) is one of the ESKAPE organisms and has the competency to build biofilms. These biofilms account for the most nosocomial infections all over the world. This review reflects on the various physicochemical and environmental factors such as adhesion, pili expression, growth surfaces, drug-resistant genes, and virulence factors that profoundly affect its resistant forte. Emerging drug-resistant issues and limitations to newer drugs are other factors affecting the hospital environment. Here, we discuss newer and alternative methods that can significantly enhance the susceptibility to Acinetobacter spp. Many new antibiotics are under trials, such as GSK-3342830, The Cefiderocol (S-649266), Fimsbactin, and similar. On the other hand, we can also see the impact of traditional medicine and the secondary metabolites of these natural products’ application in searching for new treatments. The field of nanoparticles has demonstrated effective antimicrobial actions and has exhibited encouraging results in the field of nanomedicine. The use of various phages such as vWUPSU and phage ISTD as an alternative treatment for its specificity and effectiveness is being investigated. Cathelicidins obtained synthetically or from natural sources can effectively produce antimicrobial activity in the micromolar range. Radioimmunotherapy and photodynamic therapy have boundless prospects if explored as a therapeutic antimicrobial strategy. Abstract Acinetobacter species is one of the most prevailing nosocomial pathogens with a potent ability to develop antimicrobial resistance. It commonly causes infections where there is a prolonged utilization of medical devices such as CSF shunts, catheters, endotracheal tubes, and similar. There are several strains of Acinetobacter (A) species (spp), among which the majority are pathogenic to humans, but A. baumannii are entirely resistant to several clinically available antibiotics. The crucial mechanism that renders them a multidrug-resistant strain is their potent ability to synthesize biofilms. Biofilms provide ample opportunity for the microorganisms to withstand the harsh environment and further cause chronic infections. Several studies have enumerated multiple physiological and virulence factors responsible for the production and maintenance of biofilms. To further enhance our understanding of this pathogen, in this review, we discuss its taxonomy, pathogenesis, current treatment options, global resistance rates, mechanisms of its resistance against various groups of antimicrobials, and future therapeutics.
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Affiliation(s)
- Karma G. Dolma
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India
| | - Rachana Khati
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India
| | - Alok K. Paul
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7001, Australia
| | - Mohammed Rahmatullah
- Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh
| | - Maria de Lourdes Pereira
- CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal
- Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Correspondence: (P.W.); (V.N.)
| | - Bidita Khandelwal
- Department of Medicine, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India
| | - Chamma Gupta
- Department of Biotechnology, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India
| | - Deepan Gautam
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India
| | - Madhu Gupta
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India
| | - Ramesh K. Goyal
- Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India
| | - Christophe Wiart
- Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia
| | - Veeranoot Nissapatorn
- School of Allied Health Sciences and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand
- Correspondence: (P.W.); (V.N.)
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Seo CW, Kim YK, An JL, Kim JS, Kwon PS, Yu YB. The effect of photodynamic therapy using Radachlorin on biofilm-forming multidrug-resistant bacteria. Osong Public Health Res Perspect 2022; 13:290-297. [PMID: 36097751 PMCID: PMC9468690 DOI: 10.24171/j.phrp.2022.0150] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/12/2022] [Accepted: 07/25/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES This study aimed to test the effect of photodynamic therapy (PDT) on the inhibition and removal of biofilms containing multidrug-resistant Acinetobacter baumannii. METHODS Using multidrug-resistant A. baumannii strains, an antibiotic susceptibility test was performed using the Gram-negative identification card of the Vitek 2 system (bioMérieux Inc., France), as well as an analysis of resistance genes, the effects of treatment with a light-emitting diode (LED) array using Radachlorin (RADA-PHARMA Co., Ltd., Russia), and transmission and scanning electron microscopy to confirm the biofilm-inhibitory effect of PDT. RESULTS The antibiotic susceptibility test revealed multiple resistance to the antibiotics imipenem and meropenem in the carbapenem class. A class-D-type β-lactamase was found, and OXA-23 and OXA-51 were found in 100% of 15 A. baumannii strains. After PDT using Radachlorin, morphological observations revealed an abnormal structure due to the loss of the cell membrane and extensive morphological changes, including low intracellular visibility and small vacuoles attached to the cell membrane. CONCLUSION PDT involving a combination of LED and Radachlorin significantly eliminated the biofilm of multidrug-resistant A. baumannii. Observations made using electron microscopy showed that PDT combining LED and Radachlorin was effective. Additional studies on the effective elimination of biofilms containing multidrug-resistant bacteria are necessary, and we hope that a treatment method superior to sterilization with antibiotics will be developed in the future.
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Affiliation(s)
- Choong-Won Seo
- Department of Biomedical Laboratory Science, Dongeui Institute of Technology, Busan, Korea
| | - Young-Kwon Kim
- Department of Health Sciences, The Graduate School of Konyang University, Daejeon, Korea
| | - Jeong-Lib An
- Department of Health Sciences, The Graduate School of Konyang University, Daejeon, Korea
| | - Jong-Sook Kim
- Department of Health Sciences, The Graduate School of Konyang University, Daejeon, Korea
| | - Pil-Seung Kwon
- Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Korea
| | - Young-Bin Yu
- Department of Biomedical Laboratory Science, College of Medical Sciences, Konyang University, Daejeon, Korea
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da Silva Canielles Caprara C, da Silva Freitas L, Iglesias BA, Ferreira LB, Ramos DF. Charge effect of water-soluble porphyrin derivatives as a prototype to fight infections caused by Acinetobacter baumannii by aPDT approaches. BIOFOULING 2022; 38:605-613. [PMID: 35875928 DOI: 10.1080/08927014.2022.2103804] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/28/2022] [Accepted: 07/15/2022] [Indexed: 06/15/2023]
Abstract
In the last decade, Acinetobacter baumannii has emerged as a pathogen associated with infections in intensive care units worldwide, especially due to its ability to resist an extensive list of antibiotics. In this context, porphyrins have emerged as an important strategy in photodynamic therapy, since they are a group of tetrapyrrolic compounds with important photochemical and photobiological activities. In this study, the antimicrobial photodynamic activity of meso-tetra(4-N-methyl-pyridyl)porphyrin (H2TMePyP+) and meso-tetra(4-sulfonatophenyl)porphyrin (H2TPPS‒) was evaluated against A. baumannii by minimum inhibitory concentration (MIC), anti-biofilm activity, and the interaction with antibiotics after exposure to white-light LED irradiation. The cationic derivative H2TMePyP+ was more potent (MIC = 0.61 µM) than H2TPPS‒, with anti-biofilm activity and increased the antimicrobial activity of ciprofloxacin and amikacin. Given these findings, the tetra-cationic porphyrins can be assumed as prototypes to optimize and develop new agents by promoting oxidative stress and inducing free radical production.
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Affiliation(s)
- Carolina da Silva Canielles Caprara
- Laboratório de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande (FURG) - Rio Grande, Rio Grande, Brazil
| | - Livia da Silva Freitas
- Laboratório de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande (FURG) - Rio Grande, Rio Grande, Brazil
| | - Bernardo Almeida Iglesias
- Departamento de Química, Laboratório de Bioinorgânica e Materiais Porfirínicos, Universidade Federal de Santa Maria, Santa Maria, Brazil
| | - Lara Beatriz Ferreira
- Laboratório de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande (FURG) - Rio Grande, Rio Grande, Brazil
| | - Daniela Fernandes Ramos
- Laboratório de Desenvolvimento de Novos Fármacos, Faculdade de Medicina, Universidade Federal do Rio Grande (FURG) - Rio Grande, Rio Grande, Brazil
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Figueiredo-Godoi LMA, Garcia MT, Pinto JG, Ferreira-Strixino J, Faustino EG, Pedroso LLC, Junqueira JC. Antimicrobial Photodynamic Therapy Mediated by Fotenticine and Methylene Blue on Planktonic Growth, Biofilms, and Burn Infections of Acinetobacter baumannii. Antibiotics (Basel) 2022; 11:antibiotics11050619. [PMID: 35625263 PMCID: PMC9137570 DOI: 10.3390/antibiotics11050619] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/02/2022] [Accepted: 05/02/2022] [Indexed: 11/16/2022] Open
Abstract
Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative strategy to control Acinetobacter baumannii infections. In this study, we evaluated the action of aPDT mediated by a new photosensitizer derivative from chlorin e-6 (Fotoenticine—FTC) on A. baumannii, comparing its effects with methylene blue (MB). For this, aPDT was applied on A. baumannii in planktonic growth, biofilms, and burn infections in Galleria mellonella. The absorption of FTC and MB by bacterial cells was also evaluated using microscopic and spectrophotometric analysis. The results of planktonic cultures showed that aPDT reduced the number of viable cells compared to the non-treated group for the reference and multidrug-resistant A. baumannii strains. These reductions varied from 1.4 to 2 log10 CFU for FTC and from 2 log10 CFU to total inhibition for MB. In biofilms, aPDT with MB reduced 3.9 log10 CFU of A. baumannii, whereas FTC had no effect on the cell counts. In G. mellonella, only MB-mediated aPDT had antimicrobial activity on burn injuries, increasing the larvae survival by 35%. Both photosensitizers were internalized by bacterial cells, but MB showed a higher absorption compared to FTC. In conclusion, MB had greater efficacy than FTC as a photosensitizer in aPDT against A. baumannii.
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Affiliation(s)
- Lívia M. A. Figueiredo-Godoi
- Institute of Science and Technology (ICT), São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil; (M.T.G.); (E.G.F.); (L.L.C.P.); (J.C.J.)
- Correspondence:
| | - Maíra T. Garcia
- Institute of Science and Technology (ICT), São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil; (M.T.G.); (E.G.F.); (L.L.C.P.); (J.C.J.)
| | - Juliana G. Pinto
- Photobiology Applied to Health (Photobios), University of Vale of Paraiba/UNIVAP, São José dos Campos, São Paulo 12244-000, Brazil; (J.G.P.); (J.F.-S.)
| | - Juliana Ferreira-Strixino
- Photobiology Applied to Health (Photobios), University of Vale of Paraiba/UNIVAP, São José dos Campos, São Paulo 12244-000, Brazil; (J.G.P.); (J.F.-S.)
| | - Eliseu Gabriel Faustino
- Institute of Science and Technology (ICT), São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil; (M.T.G.); (E.G.F.); (L.L.C.P.); (J.C.J.)
| | - Lara Luise Castro Pedroso
- Institute of Science and Technology (ICT), São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil; (M.T.G.); (E.G.F.); (L.L.C.P.); (J.C.J.)
| | - Juliana C. Junqueira
- Institute of Science and Technology (ICT), São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil; (M.T.G.); (E.G.F.); (L.L.C.P.); (J.C.J.)
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de Souza da Fonseca A, de Paoli F, Mencalha AL. Photodynamic therapy for treatment of infected burns. Photodiagnosis Photodyn Ther 2022; 38:102831. [PMID: 35341978 DOI: 10.1016/j.pdpdt.2022.102831] [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] [Received: 01/28/2022] [Revised: 03/17/2022] [Accepted: 03/23/2022] [Indexed: 11/30/2022]
Abstract
Burns are among the most debilitating and devastating forms of trauma. Such injuries are influenced by infections, causing increased morbidity, mortality, and healthcare costs. Due to the emergence of multidrug-resistant infectious agents, efficient treatment of infections in burns is a challenging issue. Antimicrobial photodynamic therapy (aPDT) is a promising approach to inactivate infectious agents, including multidrug-resistant. In this review, studies on PubMed were gathered, aiming to summarize the achievements regarding the applications of antimicrobial photodynamic therapy for the treatment of infected burns. A literature search was carried out for aPDT published reports assessment on bacterial, fungal, and viral infections in burns. The collected data suggest that aPDT could be a promising new approach against multidrug-resistant infectious agents. However, despite important results being obtained against bacteria, experimental and clinical studies are necessary yet on the effectiveness of aPDT against fungal and viral infections in burns, which could reduce morbidity and mortality of burned patients, mainly those infected by multidrug-resistant strains.
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Affiliation(s)
- Adenilson de Souza da Fonseca
- Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Boulevard Vinte e Oito de Setembro, 87, Fundos, Vila Isabel, Rio de Janeiro 20551030, Brazil; Departamento de Ciências Fisiológicas, Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro, Rua Frei Caneca, 94, Rio de Janeiro 20211040, Brazil; Centro de Ciências da Saúde, Centro Universitário Serra dos Órgãos, Avenida Alberto Torres, 111, Teresópolis, Rio de Janeiro 25964004, Brazil.
| | - Flavia de Paoli
- Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Rua José Lourenço Khelmer - s/n, Campus Universitário, São Pedro, Juiz de Fora, Minas Gerais 36036900, Brazil
| | - Andre Luiz Mencalha
- Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Boulevard Vinte e Oito de Setembro, 87, Fundos, Vila Isabel, Rio de Janeiro 20551030, Brazil
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10
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Heselpoth RD, Euler CW, Fischetti VA. PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections. Front Microbiol 2022; 13:817228. [PMID: 35369520 PMCID: PMC8965563 DOI: 10.3389/fmicb.2022.817228] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/27/2022] [Indexed: 11/20/2022] Open
Abstract
Most skin infections, including those complicating burns, are polymicrobial involving multiple causative bacteria. Add to this the fact that many of these organisms may be antibiotic-resistant, and a simple skin lesion or burn could soon become life-threatening. Membrane-acting cationic peptides from Gram-negative bacteriophage lysins can potentially aid in addressing the urgent need for alternative therapeutics. Such peptides natively constitute an amphipathic region within the structural composition of these lysins and function to permit outer membrane permeabilization in Gram-negative bacteria when added externally. This consequently allows the lysin to access and degrade the peptidoglycan substrate, resulting in rapid hypotonic lysis and bacterial death. When separated from the lysin, some of these cationic peptides kill sensitive bacteria more effectively than the native molecule via both outer and cytoplasmic membrane disruption. In this study, we evaluated the antibacterial properties of a modified cationic peptide from the broad-acting lysin PlyPa01. The peptide, termed PaP1, exhibited potent in vitro bactericidal activity toward numerous high priority Gram-positive and Gram-negative pathogens, including all the antibiotic-resistant ESKAPE pathogens. Both planktonic and biofilm-state bacteria were sensitive to the peptide, and results from time-kill assays revealed PaP1 kills bacteria on contact. The peptide was bactericidal over a wide temperature and pH range and could withstand autoclaving without loss of activity. However, high salt concentrations and complex matrices were found to be largely inhibitory, limiting its use to topical applications. Importantly, unlike other membrane-acting antimicrobials, PaP1 lacked cytotoxicity toward human cells. Results from a murine burn wound infection model using methicillin-resistant Staphylococcus aureus or multidrug-resistant Pseudomonas aeruginosa validated the in vivo antibacterial efficacy of PaP1. In these studies, the peptide enhanced the potency of topical antibiotics used clinically for treating chronic wound infections. Despite the necessity for additional preclinical drug development, the collective data from our study support PaP1 as a potential broad-spectrum monotherapy or adjunctive therapy for the topical treatment of polymicrobial infections and provide a foundation for engineering future lysin-derived peptides with improved antibacterial properties.
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Affiliation(s)
- Ryan D. Heselpoth
- Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, United States
- *Correspondence: Ryan D. Heselpoth,
| | - Chad W. Euler
- Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, United States
- Department of Medical Laboratory Sciences, Hunter College, New York, NY, United States
- Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, United States
| | - Vincent A. Fischetti
- Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, United States
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11
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Gomes ATPC, Faustino MAF, Neves MGPMS, Almeida A. Bioluminescent Models to Evaluate the Efficiency of Light-Based Antibacterial Approaches. Methods Mol Biol 2022; 2451:631-669. [PMID: 35505039 DOI: 10.1007/978-1-0716-2099-1_34] [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: 06/14/2023]
Abstract
The emergence of microbial resistance to antimicrobials among several common pathogenic microbial strains is an increasing problem worldwide. Thus, it is urgent to develop not only new antimicrobial therapeutics to fight microbial infections, but also new effective, rapid, and inexpensive methods to monitor the efficacy of these new therapeutics. Antimicrobial photodynamic therapy (aPDT) and antimicrobial blue light (aBL) therapy are receiving considerable attention for their antimicrobial potential and represent realistic alternatives to antibiotics. To monitor the photoinactivation process provided by aPDT and aBL, faster and more effective methods are required instead of laborious conventional plating and overnight incubation procedures. Bioluminescent microbial models are very interesting in this context. Light emission from bioluminescent microorganisms is a highly sensitive indication of their metabolic activity and can be used to monitor, in real time, the effects of antimicrobial agents and therapeutics. This chapter reviews the efforts of the scientific community concerning the development of in vitro, ex vivo, and in vivo bioluminescent bacterial models and their potential to evaluate the efficiency of aPDT and aBL in the inactivation of bacteria.
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Affiliation(s)
- Ana T P C Gomes
- Department of Biology & CESAM, University of Aveiro, Aveiro, Portugal
| | - Maria A F Faustino
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Maria G P M S Neves
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Adelaide Almeida
- Department of Biology & CESAM, University of Aveiro, Aveiro, Portugal.
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12
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Wang D, Kuzma ML, Tan X, He TC, Dong C, Liu Z, Yang J. Phototherapy and optical waveguides for the treatment of infection. Adv Drug Deliv Rev 2021; 179:114036. [PMID: 34740763 PMCID: PMC8665112 DOI: 10.1016/j.addr.2021.114036] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 10/11/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023]
Abstract
With rapid emergence of multi-drug resistant microbes, it is imperative to seek alternative means for infection control. Optical waveguides are an auspicious delivery method for precise administration of phototherapy. Studies have shown that phototherapy is promising in fighting against a myriad of infectious pathogens (i.e. viruses, bacteria, fungi, and protozoa) including biofilm-forming species and drug-resistant strains while evading treatment resistance. When administered via optical waveguides, phototherapy can treat both superficial and deep-tissue infections while minimizing off-site effects that afflict conventional phototherapy and pharmacotherapy. Despite great therapeutic potential, exact mechanisms, materials, and fabrication designs to optimize this promising treatment option are underexplored. This review outlines principles and applications of phototherapy and optical waveguides for infection control. Research advances, challenges, and outlook regarding this delivery system are rigorously discussed in a hope to inspire future developments of optical waveguide-mediated phototherapy for the management of infection and beyond.
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Affiliation(s)
- Dingbowen Wang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Michelle Laurel Kuzma
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Xinyu Tan
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province 510280, China
| | - Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA; Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Cheng Dong
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA
| | - Zhiwen Liu
- Department of Electrical Engineering, Materials Research Institute, The Pennsylvania State University, University Park, PA 16802, USA
| | - Jian Yang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
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13
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Aroso RT, Schaberle FA, Arnaut LG, Pereira MM. Photodynamic disinfection and its role in controlling infectious diseases. Photochem Photobiol Sci 2021; 20:1497-1545. [PMID: 34705261 PMCID: PMC8548867 DOI: 10.1007/s43630-021-00102-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/03/2021] [Indexed: 12/23/2022]
Abstract
Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.
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Affiliation(s)
- Rafael T Aroso
- Chemistry Department, University of Coimbra, 3004-535, Coimbra, Portugal
| | - Fábio A Schaberle
- Chemistry Department, University of Coimbra, 3004-535, Coimbra, Portugal
| | - Luís G Arnaut
- Chemistry Department, University of Coimbra, 3004-535, Coimbra, Portugal.
| | - Mariette M Pereira
- Chemistry Department, University of Coimbra, 3004-535, Coimbra, Portugal.
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14
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da Fonseca ADS, Mencalha AL, de Paoli F. Antimicrobial photodynamic therapy against Acinetobacter baumannii. Photodiagnosis Photodyn Ther 2021; 35:102430. [PMID: 34233224 DOI: 10.1016/j.pdpdt.2021.102430] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/17/2021] [Accepted: 07/01/2021] [Indexed: 01/22/2023]
Abstract
Acinetobacter baumannii (A. baumannii) has emerged as a pathogen of global importance able to cause opportunistic infections on the skin, urinary tract, lungs, and bloodstream, being frequently involved in hospital outbreaks. Such bacterium can resist a variety of environmental conditions and develop resistance to different classes of antibiotics. Antimicrobial photodynamic therapy (aPDT) has been considered a promising approach to overcome bacterial resistance once it does not cause selective environmental pressure on bacteria. In this review, studies on aPDT were accessed on PubMed, and their findings were summarized regarding its efficacy against A. baumannii. The data obtained from the literature show that exogenous photosensitizers belonging to different chemical classes are effective against multidrug-resistant A. baumannii strains. However, most of such data is from in vitro studies, and additional studies are necessary to evaluate if the exogenous photosensitizers may induce selective pressure on A. baumannii and the effectiveness of such photosensitizers in clinical practice.
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Affiliation(s)
- Adenilson de Souza da Fonseca
- Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro, 87, fundos, Vila Isabel, Rio de Janeiro, 20551030, Brazil; Departamento de Ciências Fisiológicas, Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro, Rua Frei Caneca, 94, Rio de Janeiro, 20211040, Brazil; Centro de Ciências da Saúde, Centro Universitário Serra dos Órgãos, Avenida Alberto Torres, 111, Teresópolis, Rio de Janeiro, 25964004, Brazil.
| | - Andre Luiz Mencalha
- Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro, 87, fundos, Vila Isabel, Rio de Janeiro, 20551030, Brazil
| | - Flavia de Paoli
- Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Rua José Lourenço Khelmer - s/n, Campus Universitário, São Pedro, Juiz de Fora, Minas Gerais, 36036900, Brazil
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15
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Wang Y, Li J, Geng S, Wang X, Cui Z, Ma W, Yuan M, Liu C, Ji Y. Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: An in vivo study. Photodiagnosis Photodyn Ther 2021; 34:102311. [PMID: 33930578 DOI: 10.1016/j.pdpdt.2021.102311] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 04/10/2021] [Accepted: 04/23/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM Antimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections. METHODS The cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer. RESULTS AE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald. CONCLUSIONS AE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.
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Affiliation(s)
- Yang Wang
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China
| | - Jiao Li
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China
| | - Songmei Geng
- Department of Dermatology, The Second Affiliated Hospital of College of Medicine, Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, 710004, PR China
| | - Xiaopeng Wang
- Department of Dermatology, The Second Affiliated Hospital of College of Medicine, Xi'an Jiaotong University, 157 Xi Wu Road, Xi'an, 710004, PR China
| | - Zixin Cui
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China
| | - Wenpeng Ma
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China
| | - Meng Yuan
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China
| | - Chengcheng Liu
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China.
| | - Yanhong Ji
- Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, PR China.
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16
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Vallejo MCS, Moura NMM, Gomes ATPC, Joaquinito ASM, Faustino MAF, Almeida A, Gonçalves I, Serra VV, Neves MGPMS. The Role of Porphyrinoid Photosensitizers for Skin Wound Healing. Int J Mol Sci 2021; 22:4121. [PMID: 33923523 PMCID: PMC8072979 DOI: 10.3390/ijms22084121] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/04/2021] [Accepted: 04/10/2021] [Indexed: 12/14/2022] Open
Abstract
Microorganisms, usually bacteria and fungi, grow and spread in skin wounds, causing infections. These infections trigger the immune system and cause inflammation and tissue damage within the skin or wound, slowing down the healing process. The use of photodynamic therapy (PDT) to eradicate microorganisms has been regarded as a promising alternative to anti-infective therapies, such as those based on antibiotics, and more recently, is being considered for skin wound-healing, namely for infected wounds. Among the several molecules exploited as photosensitizers (PS), porphyrinoids exhibit suitable features for achieving those goals efficiently. The capability that these macrocycles display to generate reactive oxygen species (ROS) gives a significant contribution to the regenerative process. ROS are responsible for avoiding the development of infections by inactivating microorganisms such as bacteria but also by promoting cell proliferation through the activation of stem cells which regulates inflammatory factors and collagen remodeling. The PS can act solo or combined with several materials, such as polymers, hydrogels, nanotubes, or metal-organic frameworks (MOF), keeping both the microbial photoinactivation and healing/regenerative processes' effectiveness. This review highlights the developments on the combination of PDT approach and skin wound healing using natural and synthetic porphyrinoids, such as porphyrins, chlorins and phthalocyanines, as PS, as well as the prodrug 5-aminolevulinic acid (5-ALA), the natural precursor of protoporphyrin-IX (PP-IX).
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Affiliation(s)
- Mariana C. S. Vallejo
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (M.C.S.V.); (A.S.M.J.)
| | - Nuno M. M. Moura
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (M.C.S.V.); (A.S.M.J.)
| | - Ana T. P. C. Gomes
- CESAM, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal; (A.T.P.C.G.); (A.A.)
| | - Ana S. M. Joaquinito
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (M.C.S.V.); (A.S.M.J.)
- CESAM, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal; (A.T.P.C.G.); (A.A.)
| | - Maria Amparo F. Faustino
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (M.C.S.V.); (A.S.M.J.)
| | - Adelaide Almeida
- CESAM, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal; (A.T.P.C.G.); (A.A.)
| | - Idalina Gonçalves
- CICECO, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Vanda Vaz Serra
- Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal;
| | - Maria Graça P. M. S. Neves
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (M.C.S.V.); (A.S.M.J.)
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Paolillo FR, Rodrigues PGS, Bagnato VS, Alves F, Pires L, Corazza AV. The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats. Lasers Med Sci 2020; 36:1219-1226. [PMID: 33064262 DOI: 10.1007/s10103-020-03160-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 10/12/2020] [Indexed: 10/23/2022]
Abstract
Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control-untreated; (ii) aPDT-treated with curcumin-mediated aPDT (blue light); (iii) artificial skin-treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin-treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm2) at the dose of 60 J/cm2 and the treatment with alcohol-based artificial skin was done with the topical application of 250 μL. Additional animals were submitted to aPDT combined with the artificial skin. After treatments, the number of colony-forming units (CFU) and the damage area were determined. Data were analyzed by two-way repeated measures ANOVA and Tukey tests. The highest reduction of the bacterial viability was observed in the PDT plus artificial skin group (4.14 log10), followed by artificial skin (2.38 log10) and PDT (2.22 log10) groups. In addition, all treated groups showed higher relative area of wound contraction (36.21% for the PDT, 38.41% for artificial skin, and 35.02% for PDT plus artificial) in comparison with the control group. These findings provide evidence for the positive benefits of aPDT with blue light and curcumin associated with artificial skin to decontaminate and accelerate the wound contraction.
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Affiliation(s)
- Fernanda Rossi Paolillo
- School of Physical Education, State University of Minas Gerais (UEMG), R. Colorado, 700 - Bairro São Francisco, Passos, MG, CEP 37902-092, Brazil. .,Motricity Science Institute, Rehabilitation Science Program from Federal University of Alfenas (UNIFAL), Av. Jovino Fernandes Sales, 2600 - Santa Clara, Alfenas, MG, CEP: 37133-840, Brazil. .,Optics Group from Physics Institute of São Carlos (IFSC), University of São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - Centro, São Carlos, SP, CEP 13560-970, Brazil.
| | - Phamilla Gracielli Sousa Rodrigues
- Optics Group from Physics Institute of São Carlos (IFSC), University of São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - Centro, São Carlos, SP, CEP 13560-970, Brazil
| | - Vanderlei Salvador Bagnato
- Optics Group from Physics Institute of São Carlos (IFSC), University of São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - Centro, São Carlos, SP, CEP 13560-970, Brazil
| | - Fernanda Alves
- Optics Group from Physics Institute of São Carlos (IFSC), University of São Paulo (USP), Av. Trabalhador Sãocarlense, 400 - Centro, São Carlos, SP, CEP 13560-970, Brazil
| | - Layla Pires
- Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada
| | - Adalberto Vieira Corazza
- Medical School, Federal University of Mato Grosso do Sul, Cap. Olinto Mancini Avenue, 1662 - Colinos, Três Lagoas, MS, CEP 79600-080, Brazil
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Tiganova IG, Zhizhimova YS, Philipova NI, Tolordava ER, Alekseeva NV, Makarova EA, Lukyanets EA, Meerovich GA, Romanova YM, Gintsburg AL. Antibacterial Properties of Synthetic Cationic Bacteriochlorin Derivatives as Photosensitizers. MOLECULAR GENETICS, MICROBIOLOGY AND VIROLOGY 2020. [DOI: 10.3103/s0891416820040096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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19
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Contamination of wounds with fecal bacteria in immuno-suppressed mice. Sci Rep 2020; 10:11494. [PMID: 32661287 PMCID: PMC7359036 DOI: 10.1038/s41598-020-68323-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 06/15/2020] [Indexed: 12/30/2022] Open
Abstract
Immunocompromised patients are predisposed to chronically infected wounds. Especially ulcers in the dorsal region often experience secondary polymicrobial infections. However, current wound infection models mostly use single-strain bacteria. To mimic clinically occurring infections caused by fecal contamination in immunocompromised/immobile patients, which differ significantly from single-strain infections, the present study aimed at the establishment of a new mouse model using infection by fecal bacteria. Dorsal circular excision wounds in immunosuppressed mice were infected with fecal slurry solution in several dilutions up to 1:8,000. Impact of immunosuppressor, bacterial load and timing on development of wound infections was investigated. Wounds were analyzed by scoring, 3D imaging and swab analyses. Autofluorescence imaging was not successful. Dose-finding of cyclophosphamide-induced immunosuppression was necessary for establishment of bacterial wound infections. Infection with fecal slurry diluted 1:166 to 1:400 induced significantly delayed wound healing (p < 0.05) without systemic reactions. Swab analyses post-infection matched the initial polymicrobial suspension. The customized wound score confirmed significant differences between the groups (p < 0.05). Here we report the establishment of a simple, new mouse model for clinically occurring wound infections by fecal bacteria and the evaluation of appropriate wound analysis methods. In the future, this model will provide a suitable tool for the investigation of complex microbiological interactions and evaluation of new therapeutic approaches.
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Nutman A, Lellouche J, Lifshitz Z, Glick R, Carmeli Y. In vivo Fitness of Acinetobacter baumannii Strains in Murine Infection Is Associated with International Lineage II-rep-2 and International Lineage III Clones Showing High Case Fatality Rates in Human Infections. Microorganisms 2020; 8:microorganisms8060847. [PMID: 32512869 PMCID: PMC7356693 DOI: 10.3390/microorganisms8060847] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 11/04/2022] Open
Abstract
We previously reported that the 14-day case fatality rate (CFR) in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia varied between infecting clones. Here, we evaluated the in vitro and in vivo fitness of CRAB blood isolates belonging to clones with low CFR (< 32% 14-day mortality) and high CFR (65% 14-day mortality). Fitness was measured in vitro using a growth curve assay and in vivo using murine thigh muscle and septicemia models of infection. Our sample included 38 CRAB isolates belonging to two clones with low CFR (international lineage (IL)-II-rep-1, n = 13 and IL-79, n = 6) and two clones with high CFR (IL-III, n = 9 and IL-II-rep-2, n = 10). In in vitro growth curves, mean lag time, generation time and maximal growth varied between clones but could not discriminate between the high and low CFR clones. In the in vivo models, bacterial burdens were higher in mice infected with high CFR clones than in those infected with low CFR clones: in thigh muscle, 8.78 ± 0.25 vs. 7.53 ± 0.25 log10CFU/g, p < 0.001; in infected spleen, 5.53 ± 0.38 vs. 3.71 ± 0.35 log10CFU/g, p < 0.001. The thigh muscle and septicemia model results were closely correlated (r = 0.93, p < 0.01). These results suggest that in vivo but not in vitro fitness is associated with high CFR clones.
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Affiliation(s)
- Amir Nutman
- National Institute for Infection Control and Antibiotic Resistance, Tel-Aviv Sourasky Medical Center, 6423906 Tel-Aviv, Israel; (J.L.); (Z.L.); (R.G.); (Y.C.)
- Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel
- Correspondence:
| | - Jonathan Lellouche
- National Institute for Infection Control and Antibiotic Resistance, Tel-Aviv Sourasky Medical Center, 6423906 Tel-Aviv, Israel; (J.L.); (Z.L.); (R.G.); (Y.C.)
| | - Ziv Lifshitz
- National Institute for Infection Control and Antibiotic Resistance, Tel-Aviv Sourasky Medical Center, 6423906 Tel-Aviv, Israel; (J.L.); (Z.L.); (R.G.); (Y.C.)
| | - Rivka Glick
- National Institute for Infection Control and Antibiotic Resistance, Tel-Aviv Sourasky Medical Center, 6423906 Tel-Aviv, Israel; (J.L.); (Z.L.); (R.G.); (Y.C.)
| | - Yehuda Carmeli
- National Institute for Infection Control and Antibiotic Resistance, Tel-Aviv Sourasky Medical Center, 6423906 Tel-Aviv, Israel; (J.L.); (Z.L.); (R.G.); (Y.C.)
- Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel
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21
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Braz M, Salvador D, Gomes AT, Mesquita MQ, Faustino MAF, Neves MGP, Almeida A. Photodynamic inactivation of methicillin-resistant Staphylococcus aureus on skin using a porphyrinic formulation. Photodiagnosis Photodyn Ther 2020; 30:101754. [DOI: 10.1016/j.pdpdt.2020.101754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/16/2020] [Accepted: 03/30/2020] [Indexed: 01/10/2023]
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22
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Antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii clinical isolates mediated by aloe-emodin: An in vitro study. Photodiagnosis Photodyn Ther 2020; 29:101632. [DOI: 10.1016/j.pdpdt.2019.101632] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/10/2019] [Accepted: 12/18/2019] [Indexed: 02/06/2023]
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23
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Karner L, Drechsler S, Metzger M, Hacobian A, Schädl B, Slezak P, Grillari J, Dungel P. Antimicrobial photodynamic therapy fighting polymicrobial infections – a journey from in vitro to in vivo. Photochem Photobiol Sci 2020; 19:1332-1343. [DOI: 10.1039/d0pp00108b] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The batericidal effects of antimicrobial photodynamic therapy (aPDT), using methylene blue as a photosensitizer and pulsed red LED light for activation, were tested in various environments in vitro and in a wound model in mice infected with a fecal bacterial suspension.
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Affiliation(s)
- Lisa Karner
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Susanne Drechsler
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Magdalena Metzger
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Ara Hacobian
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Barbara Schädl
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
- University Clinic of Dentistry
- Medical University of Vienna
| | - Paul Slezak
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Johannes Grillari
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
| | - Peter Dungel
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center
- Vienna
- Austria
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24
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Cabral FV, Sabino CP, Dimmer JA, Sauter IP, Cortez MJ, Ribeiro MS. Preclinical Investigation of Methylene Blue‐mediated Antimicrobial Photodynamic Therapy on
Leishmania
Parasites Using Real‐Time Bioluminescence. Photochem Photobiol 2019; 96:604-610. [DOI: 10.1111/php.13188] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 11/01/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Fernanda V. Cabral
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
| | - Caetano P. Sabino
- School of Pharmaceutical Sciences University of São Paulo São Paulo SP Brazil
- Biolambda, Translational Biophotonics LTD São Paulo SP Brazil
| | - Jesica A. Dimmer
- Pharmaceutical Sciences Department School of Chemical Sciences National University of Córdoba Córdoba Argentina
- Multidisciplinary Institute of Plant Biology (IMBIV) CONICET Córdoba Argentina
| | - Ismael P. Sauter
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
| | - Mauro J. Cortez
- Institute of Biosciences University of São Paulo (ICB/USP) São Paulo SP Brazil
| | - Martha S. Ribeiro
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
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25
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Li H, Zhong J, Zhu H, Yang Y, Ding M, Luo L, Huo Y, Li H. Hybrid Cu 2O/TiO 2 Nanocomposites with Enhanced Photocatalytic Antibacterial Activity toward Acinetobacter Baumannii. ACS APPLIED BIO MATERIALS 2019; 2:4892-4903. [PMID: 35021489 DOI: 10.1021/acsabm.9b00644] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The hybrid Cu2O-TiO2 photocatalytic composite with a p-n heterojunction was synthesized by the supercritical solvothermal route. The uniformly distributed Cu2O was stably combined with TiO2 to benefit the increase of the specific surface area, the harvesting of visible light, and the separation of photogenerated holes and electrons. As a result, photocatalytic inactivation of Acinetobacter baumannii under visible-light irradiation was facilitated. Based on the photogenerated holes acting as the main active species, the Cu2O-TiO2 photocatalytic heterojunction could induce the leakage of K+ ions and serious damage of the cell structure, leading to the final cell death. During the photoantibacterial process on Cu2O-TiO2, the RecA gene played a significant role in enhancing the survival rate of Acinetobacter baumannii. Furthermore, the great bactericidal effect of Cu2O-TiO2 nanocomposites to different bacteria indicated the potential application for the environment-friendly disinfection.
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Affiliation(s)
- Huifan Li
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Jiahui Zhong
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Huijuan Zhu
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Yuping Yang
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Mengna Ding
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Liulin Luo
- Shanghai Pulmonary Hospital, Shanghai 200433, China
| | - Yuning Huo
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
| | - Hexing Li
- The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China
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26
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Sun Y, Ogawa R, Xiao BH, Feng YX, Wu Y, Chen LH, Gao XH, Chen HD. Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies. Int Wound J 2019; 17:285-299. [PMID: 31724831 DOI: 10.1111/iwj.13269] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 01/08/2023] Open
Abstract
Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2 . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.
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Affiliation(s)
- Yan Sun
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
| | - Rei Ogawa
- Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan
| | - Bi-Huan Xiao
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
| | - Yu-Xin Feng
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
| | - Yan Wu
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
| | - Liang-Hong Chen
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xing-Hua Gao
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
| | - Hong-Duo Chen
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
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27
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Nezhadi J, Eslami H, Fakhrzadeh V, Moaddab SR, Zeinalzadeh E, Kafil HS. Photodynamic therapy of infection in burn patients. ACTA ACUST UNITED AC 2019. [DOI: 10.1097/mrm.0000000000000188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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28
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Cooper R, Kirketerp-Møller K. Non-antibiotic antimicrobial interventions and antimicrobial stewardship in wound care. J Wound Care 2019; 27:355-377. [PMID: 29883284 DOI: 10.12968/jowc.2018.27.6.355] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Control of wound infection today relies largely on antibiotics, but the continual emergence of antibiotic-resistant microorganisms threatens a return to the pre-antibiotic era when physicians used antiseptics to prevent and manage infection. Some of those antiseptics are still used today, and others have become available. A diverse variety of non-antibiotic antimicrobial interventions are found on modern formularies. Unlike the mode of action of antibiotics, which affect specific cellular target sites of pathogens, many non-antibiotic antimicrobials affect multiple cellular target sites in a non-specific way. Although this reduces the likelihood of selecting for resistant strains of microorganisms, some have emerged and cross-resistance between antibiotics and antiseptics has been detected. With the prospect of a post-antibiotic era looming, ways to maintain and extend our antimicrobial armamentarium must be found. In this narrative review, current and emerging non-antibiotic antimicrobial strategies will be considered and the need for antimicrobial stewardship in wound care will be explained.
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Affiliation(s)
- Rose Cooper
- Professor of Microbiology, Department of Biomedical Science, Cardiff School of Health Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff, UK
| | - Klaus Kirketerp-Møller
- Orthopaedic Surgeon, Copenhagen Wound Healing Center, Department of Dermatology and Wounds, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV
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29
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Figueiredo J, Serrano JL, Soares M, Ferreira S, Domingues FC, Almeida P, Silvestre S. 5-Hydrazinylethylidenepyrimidines effective against multidrug-resistant Acinetobacter baumannii: Synthesis and in vitro biological evaluation of antibacterial, radical scavenging and cytotoxic activities. Eur J Pharm Sci 2019; 137:104964. [PMID: 31233866 DOI: 10.1016/j.ejps.2019.104964] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 06/03/2019] [Accepted: 06/20/2019] [Indexed: 12/14/2022]
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30
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Khurana B, Gierlich P, Meindl A, Gomes-da-Silva LC, Senge MO. Hydrogels: soft matters in photomedicine. Photochem Photobiol Sci 2019; 18:2613-2656. [PMID: 31460568 DOI: 10.1039/c9pp00221a] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Photodynamic therapy (PDT), a shining beacon in the realm of photomedicine, is a non-invasive technique that utilizes dye-based photosensitizers (PSs) in conjunction with light and oxygen to produce reactive oxygen species to combat malignant tissues and infectious microorganisms. Yet, for PDT to become a common, routine therapy, it is still necessary to overcome limitations such as photosensitizer solubility, long-term side effects (e.g., photosensitivity) and to develop safe, biocompatible and target-specific formulations. Polymer based drug delivery platforms are an effective strategy for the delivery of PSs for PDT applications. Among them, hydrogels and 3D polymer scaffolds with the ability to swell in aqueous media have been deeply investigated. Particularly, hydrogel-based formulations present real potential to fulfill all requirements of an ideal PDT platform by overcoming the solubility issues, while improving the selectivity and targeting drawbacks of the PSs alone. In this perspective, we summarize the use of hydrogels as carrier systems of PSs to enhance the effectiveness of PDT against infections and cancer. Their potential in environmental and biomedical applications, such as tissue engineering photoremediation and photochemistry, is also discussed.
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Affiliation(s)
- Bhavya Khurana
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland.
| | - Piotr Gierlich
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland. and CQC, Coimbra Chemistry Department, University of Coimbra, Coimbra, Portugal
| | - Alina Meindl
- Physik Department E20, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany
| | | | - Mathias O Senge
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland. and Physik Department E20, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany and Institute for Advanced Study (TUM-IAS), Technische Universität München, Lichtenberg-Str. 2a, 85748 Garching, Germany
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31
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Morris FC, Dexter C, Kostoulias X, Uddin MI, Peleg AY. The Mechanisms of Disease Caused by Acinetobacter baumannii. Front Microbiol 2019; 10:1601. [PMID: 31379771 PMCID: PMC6650576 DOI: 10.3389/fmicb.2019.01601] [Citation(s) in RCA: 193] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 06/26/2019] [Indexed: 01/29/2023] Open
Abstract
Acinetobacter baumannii is a Gram negative opportunistic pathogen that has demonstrated a significant insurgence in the prevalence of infections over recent decades. With only a limited number of “traditional” virulence factors, the mechanisms underlying the success of this pathogen remain of great interest. Major advances have been made in the tools, reagents, and models to study A. baumannii pathogenesis, and this has resulted in a substantial increase in knowledge. This article provides a comprehensive review of the bacterial virulence factors, the host immune responses, and animal models applicable for the study of this important human pathogen. Collating the most recent evidence characterizing bacterial virulence factors, their cellular targets and genetic regulation, we have encompassed numerous aspects important to the success of this pathogen, including membrane proteins and cell surface adaptations promoting immune evasion, mechanisms for nutrient acquisition and community interactions. The role of innate and adaptive immune responses is reviewed and areas of paucity in our understanding are highlighted. Finally, with the vast expansion of available animal models over recent years, we have evaluated those suitable for use in the study of Acinetobacter disease, discussing their advantages and limitations.
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Affiliation(s)
- Faye C Morris
- Infection and Immunity Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
| | - Carina Dexter
- Infection and Immunity Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
| | - Xenia Kostoulias
- Infection and Immunity Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
| | - Muhammad Ikhtear Uddin
- Infection and Immunity Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
| | - Anton Y Peleg
- Infection and Immunity Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.,Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia
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32
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Marcolan De Mello M, De Barros PP, de Cassia Bernardes R, Alves SR, Ramanzini NP, Figueiredo-Godoi LMA, Prado ACC, Jorge AOC, Junqueira JC. Antimicrobial photodynamic therapy against clinical isolates of carbapenem-susceptible and carbapenem-resistant Acinetobacter baumannii. Lasers Med Sci 2019; 34:1755-1761. [DOI: 10.1007/s10103-019-02773-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 03/07/2019] [Indexed: 12/13/2022]
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33
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Wozniak A, Rapacka-Zdonczyk A, Mutters NT, Grinholc M. Antimicrobials Are a Photodynamic Inactivation Adjuvant for the Eradication of Extensively Drug-Resistant Acinetobacter baumannii. Front Microbiol 2019; 10:229. [PMID: 30814989 PMCID: PMC6381035 DOI: 10.3389/fmicb.2019.00229] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 01/28/2019] [Indexed: 12/29/2022] Open
Abstract
The worldwide emergence of extensively drug resistant (XDR) Acinetobacter baumannii has reduced the number of antimicrobials that exert high bactericidal activity against this pathogen. This is the reason why many scientists are focusing on investigations concerning novel non-antibiotic strategies such as antimicrobial photodynamic inactivation (aPDI) or the use of antimicrobial blue light (aBL). Therefore, the aim of the current study was to screen for antimicrobial synergies of routinely used antibiotics and phototherapies, including both aPDI involving exogenously administered photosensitizing molecules, namely, rose bengal, and aBL, involving excitation of endogenously produced photoactive compounds. The synergy testing was performed in accordance with antimicrobial susceptibility testing (AST) standards, including various methodological approaches, i.e., antibiotic diffusion tests, checkerboard assays, CFU counting and the evaluation of postantibiotic effects (PAEs). We report that combining antimicrobials and aPDI/aBL treatment led to a new strategy that overcomes drug resistance in XDR A. baumannii, rendering this pathogen susceptible to various categories of antibiotics. Sublethal aPDI/aBL treatment in the presence of sub-MIC levels of antimicrobials effectively killed A. baumannii expressing drug resistance to studied antibiotics when treated with only antibiotic therapy. The susceptibility of XDR A. baumannii to a range of antibiotics was enhanced following sublethal aPDI/aBL. Furthermore, 3′-(p-aminophenyl) fluorescein (APF) testing indicated that significantly increased reactive oxygen species production upon combined treatment could explain the observed synergistic activity. This result represents a conclusive example of the synergistic activity between photodynamic inactivation and clinically used antimicrobials leading to effective eradication of XDR A. baumannii isolates and indicates a potent novel therapeutic approach.
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Affiliation(s)
- Agata Wozniak
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
| | - Aleksandra Rapacka-Zdonczyk
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
| | - Nico T Mutters
- Institute for Infection Prevention and Hospital Epidemiology, Medical Center - Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Mariusz Grinholc
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
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34
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Treatment of Infected Wounds in the Age of Antimicrobial Resistance: Contemporary Alternative Therapeutic Options. Plast Reconstr Surg 2019; 142:1082-1092. [PMID: 30252823 DOI: 10.1097/prs.0000000000004799] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
As antibiotic resistance increases and antimicrobial options diminish, there is a pressing need to identify and develop new and/or alternative (non-antimicrobial-based) wound therapies. The authors describe the implications of antibiotic resistance on their current wound treatment paradigms and review the most promising non-antibiotic-based antimicrobial agents currently in research and development, with a focus on preclinical and human studies of therapeutic bacteriophages, antimicrobial peptides, cold plasma treatment, photodynamic therapy, honey, silver, and bioelectric dressings.
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35
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Xuan W, He Y, Huang L, Huang YY, Bhayana B, Xi L, Gelfand JA, Hamblin MR. Antimicrobial Photodynamic Inactivation Mediated by Tetracyclines in Vitro and in Vivo: Photochemical Mechanisms and Potentiation by Potassium Iodide. Sci Rep 2018; 8:17130. [PMID: 30459451 PMCID: PMC6244358 DOI: 10.1038/s41598-018-35594-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 11/08/2018] [Indexed: 12/19/2022] Open
Abstract
Tetracyclines (including demeclocycline, DMCT, or doxycycline, DOTC) represent a class of dual-action antibacterial compounds, which can act as antibiotics in the dark, and also as photosensitizers under illumination with blue or UVA light. It is known that tetracyclines are taken up inside bacterial cells where they bind to ribosomes. In the present study, we investigated the photochemical mechanism: Type 1 (hydroxyl radicals); Type 2 (singlet oxygen); or Type 3 (oxygen independent). Moreover, we asked whether addition of potassium iodide (KI) could potentiate the aPDI activity of tetracyclines. High concentrations of KI (200–400 mM) strongly potentiated (up to 5 logs of extra killing) light-mediated killing of Gram-negative Escherichia coli or Gram-positive MRSA (although the latter was somewhat less susceptible). KI potentiation was still apparent after a washing step showing that the iodide could penetrate the E. coli cells where the tetracycline had bound. When cells were added to the tetracycline + KI mixture after light, killing was observed in the case of E. coli showing formation of free molecular iodine. Addition of azide quenched the formation of iodine but not hydrogen peroxide. DMCT but not DOTC iodinated tyrosine. Both E. coli and MRSA could be killed by tetracyclines plus light in the absence of oxygen and this killing was not quenched by azide. A mouse model of a superficial wound infection caused by bioluminescent E. coli could be treated by topical application of DMCT and blue light and bacterial regrowth did not occur owing to the continued anti biotic activity of the tetracycline.
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Affiliation(s)
- Weijun Xuan
- Department of Otorhinolaryngology, Head and Neck Surgery, First Clinical Medical College and Hospital, Guangxi University of Chinese Medicine, Nanning, China.,Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.,Department of Dermatology, Harvard Medical School, Boston, MA, USA
| | - Ya He
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.,Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liyi Huang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.,Department of Dermatology, Harvard Medical School, Boston, MA, USA.,Department of Infectious Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Ying-Ying Huang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.,Department of Dermatology, Harvard Medical School, Boston, MA, USA
| | - Brijesh Bhayana
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
| | - Liyan Xi
- Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.,Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China
| | - Jeffrey A Gelfand
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. .,Department of Dermatology, Harvard Medical School, Boston, MA, USA. .,Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
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36
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Marković ZM, Jovanović SP, Mašković PZ, Danko M, Mičušík M, Pavlović VB, Milivojević DD, Kleinová A, Špitalský Z, Todorović Marković BM. Photo-induced antibacterial activity of four graphene based nanomaterials on a wide range of bacteria. RSC Adv 2018; 8:31337-31347. [PMID: 35548242 PMCID: PMC9085601 DOI: 10.1039/c8ra04664f] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 08/24/2018] [Indexed: 11/21/2022] Open
Abstract
Due to controversial reports concerning antibacterial activity of different graphene based materials it is very important to investigate their antibacterial action on a wide range of Gram-positive and Gram-negative bacteria. In this paper we have investigated the structure induced phototoxic antibacterial activity of four types of graphene based materials: graphene oxide (GO), graphene quantum dots (GQDs), carbon quantum dots (CQDs) and nitrogen doped carbon quantum dots (N-CQDs). Antibacterial activity was tested on 19 types of bacteria. It is found that nanometer-size CQDs and N-CQDs are the most potent agents whereas micrometer-size GO has very poor antibacterial activity. Electron paramagnetic resonance measurements confirmed photodynamic production of singlet oxygen for all types of used quantum dots. Detailed analysis has shown that N-CQDs are an excellent photodynamic antibacterial agent for treatment of bacterial infections induced by Enterobacter aerogenes (E. aerogenes), Proteus mirabilis (P. mirabilis), Staphylococcus saprophyticus (S. saprophyticus), Listeria monocytogenes (L. monocytogenes), Salmonella typhimurium (S. typhimurium) and Klebsiella pneumoniae.
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Affiliation(s)
- Zoran M Marković
- Polymer Institute, Slovak Academy of Sciences Dubravska Cesta 9 84541 Bratislava Slovakia
- Vinča Institute of Nuclear Sciences, University of Belgrade P.O.B. 522 11001 Belgrade Serbia
| | - Svetlana P Jovanović
- Vinča Institute of Nuclear Sciences, University of Belgrade P.O.B. 522 11001 Belgrade Serbia
| | - Pavle Z Mašković
- The Faculty of Agronomy Čačak, University of Kragujevac Cara Dušana 34 32000 Čačak Serbia
| | - Martin Danko
- Polymer Institute, Slovak Academy of Sciences Dubravska Cesta 9 84541 Bratislava Slovakia
| | - Matej Mičušík
- Polymer Institute, Slovak Academy of Sciences Dubravska Cesta 9 84541 Bratislava Slovakia
| | - Vladimir B Pavlović
- Faculty of Agriculture, Department of Agricultural Engineering, University of Belgrade, Nemanjina 6 Zemun 11080 Serbia
| | - Dušan D Milivojević
- Vinča Institute of Nuclear Sciences, University of Belgrade P.O.B. 522 11001 Belgrade Serbia
| | - Angela Kleinová
- Polymer Institute, Slovak Academy of Sciences Dubravska Cesta 9 84541 Bratislava Slovakia
| | - Zdeno Špitalský
- Polymer Institute, Slovak Academy of Sciences Dubravska Cesta 9 84541 Bratislava Slovakia
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Yang MJ, Hung YA, Wong TW, Lee NY, Yuann JMP, Huang ST, Wu CY, Chen IZ, Liang JY. Effects of Blue-Light-Induced Free Radical Formation from Catechin Hydrate on the Inactivation of Acinetobacter baumannii, Including a Carbapenem-Resistant Strain. Molecules 2018; 23:molecules23071631. [PMID: 29973539 PMCID: PMC6100571 DOI: 10.3390/molecules23071631] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 06/29/2018] [Accepted: 07/02/2018] [Indexed: 01/22/2023] Open
Abstract
Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O2•−), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)—including a carbapenem-resistant A. baumannii (CRAB)—was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O2•− was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms.
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Affiliation(s)
- Meei-Ju Yang
- Tea Research and Extension Station, Taoyuan 32654, Taiwan.
| | - Yi-An Hung
- Department of Biotechnology, Ming-Chuan University, Gui-Shan 33343, Taiwan.
| | - Tak-Wah Wong
- Department of Dermatology, Department of Biochemistry and Molecular Biology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| | - Nan-Yao Lee
- Division of Infection, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| | - Jeu-Ming P Yuann
- Department of Biotechnology, Ming-Chuan University, Gui-Shan 33343, Taiwan.
| | - Shiuh-Tsuen Huang
- Department of Science Education and Application, National Taichung University of Education, Taichung 40306, Taiwan.
| | - Chun-Yi Wu
- Department of Biotechnology, Ming-Chuan University, Gui-Shan 33343, Taiwan.
| | - Iou-Zen Chen
- Department of Horticulture and Landscape Architecture, National Taiwan University, Taipei 10617, Taiwan.
| | - Ji-Yuan Liang
- Department of Biotechnology, Ming-Chuan University, Gui-Shan 33343, Taiwan.
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38
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Bahador A, Farshadzadeh Z, Raoofian R, Mokhtaran M, Pourakbari B, Pourhajibagher M, Hashemi FB. Association of virulence gene expression with colistin-resistance in Acinetobacter baumannii: analysis of genotype, antimicrobial susceptibility, and biofilm formation. Ann Clin Microbiol Antimicrob 2018; 17:24. [PMID: 29859115 PMCID: PMC5984448 DOI: 10.1186/s12941-018-0277-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 05/19/2018] [Indexed: 12/01/2022] Open
Abstract
Background Acinetobacter baumannii causes difficult-to-treat nosocomial infections, which often lead to morbidity due to the development of antimicrobial drug resistance and expression of virulence genes. Data regarding the association of resistance to colistin, a last treatment option, and the virulence gene expression of A. baumannii is scarce. Methods We evaluated the MLVA genotype, antimicrobial resistance, and biofilm formation of 100 A. baumannii isolates from burn patients, and further compared the in vitro and in vivo expression of four virulence genes among five colistin-resistant A. baumannii (Cst-R-AB) isolates. Five Cst-R-AB isolates were tested; one from the present study, and four isolated previously. Results Our results showed that reduced expression of recA, along with increased in vivo expression of lpsB, dnaK, and blsA; are associated with colistin resistance among Cst-R-AB isolates. Differences in virulence gene expressions among Cst-R-AB isolates, may in part explain common discrepant in vitro vs. in vivo susceptibility data during treatment of infections caused by Cst-R-AB. Conclusions Our findings highlight the intricate relationship between colistin-resistance and virulence among A. baumannii isolates, and underscore the importance of examining the interactions between virulence and antimicrobial resistance toward efforts to control the spread of multidrug-resistant A. baumannii (MDR-AB) isolates, and also to reduce disease severity in burn patients with MDR-AB infection. Electronic supplementary material The online version of this article (10.1186/s12941-018-0277-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Abbas Bahador
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, 100 Poursina Ave., 100 Keshavarz Blvd, Tehran, 14167-53955, Iran.,Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.,Laser Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Farshadzadeh
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, 100 Poursina Ave., 100 Keshavarz Blvd, Tehran, 14167-53955, Iran
| | - Reza Raoofian
- Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.,Innovative Research Center, Islamic Azad University, Mashhad Branch, Mashhad, Iran
| | - Masoumeh Mokhtaran
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, 100 Poursina Ave., 100 Keshavarz Blvd, Tehran, 14167-53955, Iran
| | - Babak Pourakbari
- Pediatrics Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Pourhajibagher
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, 100 Poursina Ave., 100 Keshavarz Blvd, Tehran, 14167-53955, Iran.,Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farhad B Hashemi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, 100 Poursina Ave., 100 Keshavarz Blvd, Tehran, 14167-53955, Iran.
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Pereira AHC, Pinto JG, Freitas MAA, Fontana LC, Pacheco Soares C, Ferreira-Strixino J. Methylene blue internalization and photodynamic action against clinical and ATCC Pseudomonas aeruginosa and Staphyloccocus aureus strains. Photodiagnosis Photodyn Ther 2018; 22:43-50. [DOI: 10.1016/j.pdpdt.2018.02.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 01/26/2018] [Accepted: 02/09/2018] [Indexed: 12/19/2022]
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40
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Wozniak A, Grinholc M. Combined Antimicrobial Activity of Photodynamic Inactivation and Antimicrobials-State of the Art. Front Microbiol 2018; 9:930. [PMID: 29867839 PMCID: PMC5952179 DOI: 10.3389/fmicb.2018.00930] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 04/20/2018] [Indexed: 11/13/2022] Open
Abstract
Antimicrobial photodynamic inactivation (aPDI) is a promising tool for the eradication of life-threatening pathogens with different profiles of resistance. This study presents the state-of-the-art published studies that have been dedicated to analyzing the bactericidal effects of combining aPDI and routinely applied antibiotics in in vitro (using biofilm and planktonic cultures) and in vivo experiments. Furthermore, the current paper reviews the methodology used to obtain the published data that describes the synergy between these antimicrobial approaches. The authors are convinced that even though the combined efficacy of aPDI and antimicrobials could be investigated with the wide range of methods, the use of a unified experimental methodology that is in agreement with antimicrobial susceptibility testing (AST) is required to investigate possible synergistic cooperation between aPDI and antimicrobials. Conclusions concerning the possible synergistic activity between the two treatments can be drawn only when appropriate assays are employed. It must be noticed that some of the described papers were just aimed at determination if combined treatments exert enhanced antibacterial outcome, without following the standard methodology to evaluate the synergistic effect, but in most of them (18 out of 27) authors indicated the existence of synergy between described antibacterial approaches. In general, the increase in bacterial inactivation was observed when both therapies were used in combination.
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Affiliation(s)
- Agata Wozniak
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
| | - Mariusz Grinholc
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
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41
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Ahmed I, Fang Y, Lu M, Yan Q, Kamel AEHM, Hamblin MR, Dai T. Recent Patents on Light-Based Anti-Infective Approaches. RECENT PATENTS ON ANTI-INFECTIVE DRUG DISCOVERY 2018; 13:70-88. [PMID: 29119936 PMCID: PMC5938159 DOI: 10.2174/1872213x11666171108104104] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 10/17/2017] [Accepted: 10/29/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based anti-infective therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains. This method includes utilizing antimicrobial blue light, antimicrobial photodynamic therapy, and germicidal ultraviolet irradiation, among others. Light-based therapy is advantageous over traditional antibiotics in that it eradicates microbial cells rapidly and the likelihood of light-resistance development by microbes is low. METHODS This review highlights the patents on light-based therapy that were filed approximately within the last decade and are dedicated to eradicating pathogenic microorganisms. The primary database that was used for the search was Google Patents. The searches were performed using the keywords including blue light, antimicrobial photodynamic therapy, ultraviolet irradiation, antibiotic resistance, disinfection, bacterium, fungus, and virus. RESULTS Forty-five patents were obtained in our search: 9 patents for the antimicrobial blue light approach, 21 for antimicrobial photodynamic therapy, 11 for UV irradiation, and lastly 4 for other light-based anti-infective approaches. The treatments and devices discussed in this review are interestingly enough able to be used in various different functions and settings, such as dental applications, certain eye diseases, skin and hard surface cleansing, decontamination of internal organs (e.g., the stomach), decontamination of apparel and equipment, eradication of pathogenic microorganisms from buildings and rooms, etc. Most of the devices and inventions introduce methods of destroying pathogenic bacteria and fungi without harming human cells and tissues. CONCLUSIONS Light-based antimicrobial approaches hold great promise for the future in regards to treating antibiotic-resistant infections and related diseases.
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Affiliation(s)
- Imran Ahmed
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Yanyan Fang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Min Lu
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Quan Yan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ahmed El-Hussein Mohamed Kamel
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Biotechnology, National Institute of Laser Enhanced Science, Cairo University, Cairo, Egypt
| | - Michael R. Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Tianhong Dai
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Kielmann M, Prior C, Senge MO. Porphyrins in troubled times: a spotlight on porphyrins and their metal complexes for explosives testing and CBRN defense. NEW J CHEM 2018. [DOI: 10.1039/c7nj04679k] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A critical perspective on (metallo)porphyrins in security-related applications: the past, present and future of explosives detection, CBRN defense, and beyond.
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Affiliation(s)
- Marc Kielmann
- School of Chemistry
- SFI Tetrapyrrole Laboratory
- Trinity Biomedical Sciences Institute
- Trinity College Dublin
- The University of Dublin
| | - Caroline Prior
- School of Chemistry
- SFI Tetrapyrrole Laboratory
- Trinity Biomedical Sciences Institute
- Trinity College Dublin
- The University of Dublin
| | - Mathias O. Senge
- Medicinal Chemistry
- Trinity Translational Medicine Institute
- Trinity Centre for Health Sciences
- Trinity College Dublin
- The University of Dublin
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43
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Staegemann MH, Gräfe S, Gitter B, Achazi K, Quaas E, Haag R, Wiehe A. Hyperbranched Polyglycerol Loaded with (Zinc-)Porphyrins: Photosensitizer Release Under Reductive and Acidic Conditions for Improved Photodynamic Therapy. Biomacromolecules 2017; 19:222-238. [DOI: 10.1021/acs.biomac.7b01485] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Michael H. Staegemann
- Institut
für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany
- Biolitec Research GmbH, Otto-Schott-Str.
15, D-07745 Jena, Germany
| | - Susanna Gräfe
- Biolitec Research GmbH, Otto-Schott-Str.
15, D-07745 Jena, Germany
| | - Burkhard Gitter
- Biolitec Research GmbH, Otto-Schott-Str.
15, D-07745 Jena, Germany
| | - Katharina Achazi
- Institut
für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany
| | - Elisa Quaas
- Institut
für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany
| | - Rainer Haag
- Institut
für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany
| | - Arno Wiehe
- Institut
für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany
- Biolitec Research GmbH, Otto-Schott-Str.
15, D-07745 Jena, Germany
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Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR. In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence 2017; 9:28-63. [PMID: 28960132 PMCID: PMC6067836 DOI: 10.1080/21505594.2017.1371897] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However, the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. BLI technology has been used to follow bacterial infections in traumatic skin wounds and burns, osteomyelitis, infections in intestines, Mycobacterial infections, otitis media, lung infections, biofilm and endodontic infections and meningitis. Fungi that have been engineered to be bioluminescent have been used to study infections caused by yeasts (Candida) and by filamentous fungi. Parasitic infections caused by malaria, Leishmania, trypanosomes and toxoplasma have all been monitored by BLI. Viruses such as vaccinia, herpes simplex, hepatitis B and C and influenza, have been studied using BLI. This rapidly growing technology is expected to continue to provide much useful information, while drastically reducing the numbers of animals needed in experimental studies.
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Affiliation(s)
- Pinar Avci
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,b Department of Dermatology , Harvard Medical School , Boston , MA , USA
| | - Mahdi Karimi
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,c Department of Medical Nanotechnology , School of Advanced Technologies in Medicine, Iran University of Medical Sciences , Tehran , Iran.,d Cellular and Molecular Research Center, Iran University of Medical Sciences , Tehran , Iran
| | - Magesh Sadasivam
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,e Amity Institute of Nanotechnology, Amity University Uttar Pradesh , Noida , India
| | - Wanessa C Antunes-Melo
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,f University of Sao Paulo , Sao Carlos-SP , Brazil
| | - Elisa Carrasco
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,g Department of Biosciences , Durham University , Durham , United Kingdom
| | - Michael R Hamblin
- a Wellman Center for Photomedicine, Massachusetts General Hospital , Boston , MA , USA.,b Department of Dermatology , Harvard Medical School , Boston , MA , USA.,h Harvard-MIT Division of Health Sciences and Technology , Cambridge , MA , USA
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45
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Hamblin MR. Potentiation of antimicrobial photodynamic inactivation by inorganic salts. Expert Rev Anti Infect Ther 2017; 15:1059-1069. [PMID: 29084463 DOI: 10.1080/14787210.2017.1397512] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Antimicrobial photodynamic inactivation (aPDI) involves the use of non-toxic dyes excited with visible light to produce reactive oxygen species (ROS) that can destroy all classes of microorganisms including bacteria, fungi, parasites, and viruses. Selectivity of killing microbes over host mammalian cells allows this approach (antimicrobial photodynamic therapy, aPDT) to be used in vivo as an alternative therapeutic approach for localized infections especially those that are drug-resistant. Areas covered: We have discovered that aPDI can be potentiated (up to 6 logs of extra killing) by the addition of simple inorganic salts. The most powerful and versatile salt is potassium iodide, but potassium bromide, sodium thiocyanate, sodium azide and sodium nitrite also show potentiation. The mechanism of potentiation with iodide is likely to be singlet oxygen addition to iodide to form iodine radicals, hydrogen peroxide and molecular iodine. Another mechanism involves two-electron oxidation of iodide/bromide to form hypohalites. A third mechanism involves a one-electron oxidation of azide anion to form azide radical. Expert commentary: The addition of iodide has been shown to improve the performance of aPDT in several animal models of localized infection. KI is non-toxic and is an approved drug for antifungal therapy, so its transition to clinical use in aPDT should be straightforward.
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Affiliation(s)
- Michael R Hamblin
- a Massachusetts General Hospital , Wellman Center for Photomedicine , Boston , MA , USA
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46
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Fila G, Kawiak A, Grinholc MS. Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors. Virulence 2017; 8:938-958. [PMID: 27763824 PMCID: PMC5626244 DOI: 10.1080/21505594.2016.1250995] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 10/12/2016] [Accepted: 10/15/2016] [Indexed: 01/16/2023] Open
Abstract
Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.
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Affiliation(s)
- Grzegorz Fila
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
| | - Anna Kawiak
- Division of Plant Protection and Biotechnology, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
- Laboratory of Human Physiology, Medical University of Gdansk, Gdansk, Poland
| | - Mariusz Stanislaw Grinholc
- Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
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47
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Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies. Antimicrob Agents Chemother 2017; 61:AAC.00467-17. [PMID: 28438946 DOI: 10.1128/aac.00467-17] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 04/19/2017] [Indexed: 02/05/2023] Open
Abstract
Rose bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While RB is highly active against Gram-positive bacteria, it is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the nontoxic salt potassium iodide (100 mM) potentiates green light (540-nm)-mediated killing by up to 6 extra logs with the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium methicillin-resistant Staphylococcus aureus, and the fungal yeast Candida albicans The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals and, finally, forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing the levels of killing achieved in three different scenarios: (i) cells, RB, and KI are mixed together and then illuminated with green light; (ii) cells and RB are centrifuged, and then KI is added and the mixture is illuminated with green light; and (iii) RB and KI are illuminated with green light, and then cells are added after illumination with the light. We also showed that KI could potentiate RB photodynamic therapy in a mouse model of skin abrasions infected with bioluminescent P. aeruginosa.
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48
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Yuan Y, Liu ZQ, Jin H, Sun S, Liu TJ, Wang X, Fan HJ, Hou SK, Ding H. Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies. PLoS One 2017; 12:e0176529. [PMID: 28493985 PMCID: PMC5426629 DOI: 10.1371/journal.pone.0176529] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 04/12/2017] [Indexed: 12/31/2022] Open
Abstract
Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.
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Affiliation(s)
- Yao Yuan
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
| | - Zi-Quan Liu
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
| | - Heng Jin
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Shi Sun
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Tian-Jun Liu
- Tianjin Key Laboratory of Biomedical Material, Institute of Biomedical Engineering, Peking Union Medical College – Chinese Academy of Medical Sciences, Tianjin, China
| | - Xue Wang
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
| | - Hao-Jun Fan
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
| | - Shi-Ke Hou
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
| | - Hui Ding
- Institute of Disaster Medicine and Public Health, Affiliated Hospital of Logistic University of the Chinese People’s Armed Police Force (PAP), Tianjin, China
- * E-mail:
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49
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Wang Y, Harrington OD, Wang Y, Murray CK, Hamblin MR, Dai T. In Vivo Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant Acinetobacter baumannii Burn Infections Using Bioluminescence Imaging. J Vis Exp 2017. [PMID: 28518072 DOI: 10.3791/54997] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Burn infections continue to be an important cause of morbidity and mortality. The increasing emergence of multidrug-resistant (MDR) bacteria has led to the frequent failure of traditional antibiotic treatments. Alternative therapeutics are urgently needed to tackle MDR bacteria. An innovative non-antibiotic approach, antimicrobial blue light (aBL), has shown promising effectiveness against MDR infections. The mechanism of action of aBL is not yet well understood. It is commonly hypothesized that naturally occurring endogenous photosensitizing chromophores in bacteria (e.g., iron-free porphyrins, flavins, etc.) are excited by aBL, which in turn produces cytotoxic reactive oxygen species (ROS) through a photochemical process. Unlike another light-based antimicrobial approach, antimicrobial photodynamic therapy (aPDT), aBL therapy does not require the involvement of an exogenous photosensitizer. All it needs to take effect is the irradiation of blue light; therefore, it is simple and inexpensive. The aBL receptors are the endogenous cellular photosensitizers in bacteria, rather than the DNA. Thus, aBL is believed to be much less genotoxic to host cells than ultraviolet-C (UVC) irradiation, which directly causes DNA damage in host cells. In this paper, we present a protocol to assess the effectiveness of aBL therapy for MDR Acinetobacter baumannii infections in a mouse model of burn injury. By using an engineered bioluminescent strain, we were able to noninvasively monitor the extent of infection in real time in living animals. This technique is also an effective tool for monitoring the spatial distribution of infections in animals.
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Affiliation(s)
- Yucheng Wang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School; Department of Medical Oncology, Beijing Institute of Translational Medicine, Chinese Academy of Sciences; Cancer Center, Aviation General Hospital, Beijing
| | - Olivia D Harrington
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
| | - Ying Wang
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
| | | | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
| | - Tianhong Dai
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School;
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Staegemann MH, Gitter B, Dernedde J, Kuehne C, Haag R, Wiehe A. Mannose-Functionalized Hyperbranched Polyglycerol Loaded with Zinc Porphyrin: Investigation of the Multivalency Effect in Antibacterial Photodynamic Therapy. Chemistry 2017; 23:3918-3930. [PMID: 28029199 DOI: 10.1002/chem.201605236] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Indexed: 02/03/2023]
Abstract
The antibacterial photodynamic activity of hyperbranched polyglycerol (hPG) loaded with zinc porphyrin photosensitizers and mannose units was investigated. hPG, with a MW of 19.5 kDa, was functionalized with about 15 molecules of the photosensitizer {5,10,15-tris(3-hydroxyphenyl)-20-[4-(prop-2-yn-1-ylamino)tetrafluorophenyl]porphyrinato}-zinc(II) by using copper(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC). These nanoparticle conjugates were functionalized systematically with increasing loadings of mannose in the range of approximately 20 to 110 groups. With higher mannose loadings (ca. 58-110 groups) the water-insoluble zinc porphyrin photosensitizer could thus be transferred into a water-soluble form. Targeting of the conjugates was proven in binding studies to the mannose-specific lectin concanavalin A (Con A) by using surface plasmon resonance (SPR). The antibacterial phototoxicity of the conjugates on Staphylococcus aureus (as a typical Gram-positive germ) was investigated in phosphate-buffered saline (PBS). It was shown that conjugates with approximately 70-110 mannose units exhibit significant antibacterial activity, whereas conjugates with approximately 20-60 units did not induce bacterial killing at all. These results give an insight into the multivalency effect in combination with photodynamic therapy (PDT). On addition of serum to the bacterial cultures, a quenching of this antibacterial phototoxicity was observed. In fluorescence studies with the conjugates in the presence of increasing bovine serum albumin (BSA) concentrations, protein-conjugate associations could be identified as a plausible cause for this quenching.
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Affiliation(s)
- Michael H Staegemann
- Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany
| | - Burkhard Gitter
- Biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany
| | - Jens Dernedde
- Charité-Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Christian Kuehne
- Charité-Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Rainer Haag
- Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany
| | - Arno Wiehe
- Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.,Biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany
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