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Xiao Y, Zhang B, Zhang H, Zhang Z, Meng F, Zhao X, Zhang J, Xiao D. Study of the relationships among known virulence genes, coccoid transformation and cytotoxicity of Helicobacter pylori in different clinical diseases. Virulence 2024; 15:2418407. [PMID: 39420787 PMCID: PMC11497995 DOI: 10.1080/21505594.2024.2418407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/31/2024] [Accepted: 08/13/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori. METHODS The known important virulence genes of 35 H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) were infected with H. pylori strains in vitro to evaluate cytotoxicity of H. pylori. RESULTS There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori. CONCLUSIONS Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori. However, the correlation between the new virulence classification and pathogenic ability still needs to be further verified.
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Affiliation(s)
- Yao Xiao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Binghua Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Huifang Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Zehui Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fanliang Meng
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Xin Zhao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianzhong Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Di Xiao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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Fauzia KA, Effendi WI, Alfaray RI, Malaty HM, Yamaoka Y, Mifthussurur M. Molecular Mechanisms of Biofilm Formation in Helicobacter pylori. Antibiotics (Basel) 2024; 13:976. [PMID: 39452242 PMCID: PMC11504965 DOI: 10.3390/antibiotics13100976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 10/11/2024] [Accepted: 10/12/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. METHODS We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. RESULTS The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. CONCLUSIONS This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection.
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Grants
- XXXX Universitas Airlangga
- DK62813 NIH HHS
- 26640114, 221S0002, 16H06279, 15H02657 and 16H05191, 18KK0266, 19H03473, 21H00346, 22H02871, and 23K24133 Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- XXXXX Japan Society for the Promotion of Science Institutional Program for Young Researcher Overseas Visits and the Strategic Funds for the Promotion of Science and Technology Agency (JST)
- xxxx Japanese Government (MEXT) scholarship
- xxxx Japan Agency for Medical Research and Development (AMED) [e-ASIA JRP]
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Affiliation(s)
- Kartika Afrida Fauzia
- Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency, Bogor 16915, Indonesia;
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60131, Indonesia
| | - Wiwin Is Effendi
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine—The Research Center for GLOBAL and LOCAL Infectious Disease (RCGLID), Faculty of Medicine, Oita University, Yufu 879-5593, Japan; (R.I.A.); (Y.Y.)
| | - Hoda M. Malaty
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine—Dr. Soetomo Teaching Hospital, Univcersitas Airlangga, Surabaya 60286, Indonesia
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine—The Research Center for GLOBAL and LOCAL Infectious Disease (RCGLID), Faculty of Medicine, Oita University, Yufu 879-5593, Japan; (R.I.A.); (Y.Y.)
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine—Dr. Soetomo Teaching Hospital, Univcersitas Airlangga, Surabaya 60286, Indonesia
| | - Muhammad Mifthussurur
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya 60131, Indonesia
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;
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Huang TT, Cao YX, Cao L. Novel therapeutic regimens against Helicobacter pylori: an updated systematic review. Front Microbiol 2024; 15:1418129. [PMID: 38912349 PMCID: PMC11190606 DOI: 10.3389/fmicb.2024.1418129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were "H. pylori", "H. pylori infection", "H. pylori diseases", "H. pylori eradication", and "H. pylori antibacterial resistance." Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.
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Affiliation(s)
- Ting-Ting Huang
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Yong-Xiao Cao
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Lei Cao
- Precision Medical Institute, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Brkić N, Švagelj D, Omazić J. Pathohistological Changes in the Gastric Mucosa in Correlation with the Immunohistochemically Detected Spiral and Coccoid Forms of Helicobacter pylori. Microorganisms 2024; 12:1060. [PMID: 38930442 PMCID: PMC11206044 DOI: 10.3390/microorganisms12061060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND The coccoid form of Helicobacter pylori (H. pylori) is resistant to antibiotics. There are only a few studies that have analyzed the frequency of coccoid H. pylori in patients with gastritis. The aim of this work was to examine the correlation between the H. pylori form and the pathohistological characteristics of the stomach in patients with gastritis. MATERIALS AND METHODS This research was cross-sectional and focused on the gastric mucosa samples of 397 patients from one general hospital in Croatia. Two independent pathologists analyzed the samples regarding the pathohistological characteristics and the form of H. pylori. RESULTS There was a statistically significant difference in the gender of patients with H. pylori gastritis. Only the coccoid form of H. pylori was present in 9.6% of patients. There was a statistically significant difference in the frequency of a certain form of the bacterium depending on its localization in the stomach. The intensity of the bacterium was low in the samples where only the coccoid or spiral form was described. In cases of infection in the antrum, premalignant lesions and the coccoid form of H. pylori were more often present. CONCLUSION In the diagnosis of H. pylori infection, the determination of the form of the bacterium via immunohistochemistry should be included to increase the rate of eradication therapy and reduce the incidence of gastric malignancy.
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Affiliation(s)
- Nikolina Brkić
- Faculty of Medicine, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia;
- Department of Transfusion Medicine, General County Hospital Vinkovci, 32100 Vinkovci, Croatia
| | - Dražen Švagelj
- Department of Pathology and Cytology, General County Hospital Vinkovci, 32100 Vinkovci, Croatia;
| | - Jelena Omazić
- Faculty of Medicine, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia;
- Department of Laboratory and Transfusion Medicine, National Memorial Hospital “Dr. Jurjaj Njavro” Vukovar, 32000 Vukovar, Croatia
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Sharma A, Singh AK, Muthukumaran J, Jain M. Targeting MurB from
Helicobacter pylori
: insights from virtual screening, molecular docking and molecular dynamics simulation. MOLECULAR SIMULATION 2024; 50:379-393. [DOI: 10.1080/08927022.2024.2316818] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/02/2024] [Indexed: 01/03/2025]
Affiliation(s)
- Abhishek Sharma
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Amit Kumar Singh
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Jayaraman Muthukumaran
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Monika Jain
- Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India
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Barrett KA, Kassama FJ, Surks W, Mulholland AJ, Moulton KD, Dube DH. Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response. Front Cell Infect Microbiol 2024; 14:1377077. [PMID: 38572314 PMCID: PMC10987845 DOI: 10.3389/fcimb.2024.1377077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 03/11/2024] [Indexed: 04/05/2024] Open
Abstract
Introduction The pathogenic bacterium Helicobacter pylori has evolved glycan-mediated mechanisms to evade host immune defenses. This study tests the hypothesis that genetic disruption of H. pylori glycan biosynthesis alters immune recognition and response by human gastric epithelial cells and monocyte-derived dendritic cells. Methods To test this hypothesis, human cell lines were challenged with wildtype H. pylori alongside an array of H. pylori glycosylation mutants. The relative levels of immune response were measured via immature dendritic cell maturation and cytokine secretion. Results Our findings indicate that disruption of lipopolysaccharide biosynthesis diminishes gastric cytokine production, without disrupting dendritic cell recognition and activation. In contrast, variable immune responses were observed in protein glycosylation mutants which prompted us to test the hypothesis that phase variation plays a role in regulating bacterial cell surface glycosylation and subsequent immune recognition. Lewis antigen presentation does not correlate with extent of immune response, while the extent of lipopolysaccharide O-antigen elaboration does. Discussion The outcomes of this study demonstrate that H. pylori glycans modulate the host immune response. This work provides a foundation to pursue immune-based tailoring of bacterial glycans towards modulating immunogenicity of microbial pathogens.
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Affiliation(s)
| | | | | | | | | | - Danielle H. Dube
- Department of Chemistry & Biochemistry, Bowdoin College, Brunswick, ME, United States
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Lim NR, Kim J, Chung WC. Recurrence of Helicobacter pylori following successful eradication and clinical outcomes in Korean patients. Helicobacter 2024; 29:e13036. [PMID: 37985416 DOI: 10.1111/hel.13036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 10/26/2023] [Accepted: 10/30/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND/AIMS Helicobacter pylori (H. pylori) infections can recur as either recrudescence or reinfection. At a time when the decline in the eradication rate is becoming evident, increases in the rate of recurrence are concerning. In addition, there are no guidelines for selecting an eradication regimen for H. pylori recurrence. MATERIALS AND METHODS A total of 996 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy between 2017 and 2022 were enrolled in the study, and successful eradication therapies were confirmed by the 13 C-urea breath test. When retested within 1 year after successful eradication, analysis related to recrudescence was performed, and when retested after 1 year, analysis related to reinfection was performed. We reviewed the medical records and treatment outcomes of patients with H. pylori reinfection after successful eradication. RESULTS The recrudescence rate was 3.9% (9/228), and the reinfection rate was 3.7% (36/970 person-year). The frequency of reinfection reached 5.9% per person-year within the first 24 months and 2.0%-2.4% per person-year thereafter. In multivariate factor analysis, reinfection was significantly higher in patients with non-ulcer dyspepsia (p < 0.01). At first-line therapy for reinfection, the eradication rate of standard triple therapy (STT) was 50.0% (16/32). The eradication rate of second-line bismuth quadruple therapy was 81.3% (13/16), and levofloxacin-based rescue therapy was 66.7% (2/3). CONCLUSION Re-treatment of patients with H. pylori reinfection with STT had limited efficacy. Prospective research is needed to determine whether patients with non-ulcer dyspepsia are vulnerable to reinfection.
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Affiliation(s)
- Na Rae Lim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Suwon, South Korea
| | - Jiyoung Kim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Suwon, South Korea
| | - Woo Chul Chung
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea, Suwon, South Korea
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López-Luis MA, Soriano-Pérez EE, Parada-Fabián JC, Torres J, Maldonado-Rodríguez R, Méndez-Tenorio A. A Proposal for a Consolidated Structural Model of the CagY Protein of Helicobacter pylori. Int J Mol Sci 2023; 24:16781. [PMID: 38069104 PMCID: PMC10706595 DOI: 10.3390/ijms242316781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/17/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
CagY is the largest and most complex protein from Helicobacter pylori's (Hp) type IV secretion system (T4SS), playing a critical role in the modulation of gastric inflammation and risk for gastric cancer. CagY spans from the inner to the outer membrane, forming a channel through which Hp molecules are injected into human gastric cells. Yet, a tridimensional structure has been reported for only short segments of the protein. This intricate protein was modeled using different approaches, including homology modeling, ab initio, and deep learning techniques. The challengingly long middle repeat region (MRR) was modeled using deep learning and optimized using equilibrium molecular dynamics. The previously modeled segments were assembled into a 1595 aa chain and a 14-chain CagY multimer structure was assembled by structural alignment. The final structure correlated with published structures and allowed to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric cells. The model confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain may function as a contractile region playing an essential role in the modulating activity of CagY on tissue inflammation.
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Affiliation(s)
- Mario Angel López-Luis
- Laboratorio de Biotecnología y Bioinformática Genómica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Lázaro Cárdenas, Mexico City 11340, Mexico; (M.A.L.-L.); (E.E.S.-P.); (J.C.P.-F.); (R.M.-R.)
| | - Eva Elda Soriano-Pérez
- Laboratorio de Biotecnología y Bioinformática Genómica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Lázaro Cárdenas, Mexico City 11340, Mexico; (M.A.L.-L.); (E.E.S.-P.); (J.C.P.-F.); (R.M.-R.)
| | - José Carlos Parada-Fabián
- Laboratorio de Biotecnología y Bioinformática Genómica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Lázaro Cárdenas, Mexico City 11340, Mexico; (M.A.L.-L.); (E.E.S.-P.); (J.C.P.-F.); (R.M.-R.)
| | - Javier Torres
- Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico;
| | - Rogelio Maldonado-Rodríguez
- Laboratorio de Biotecnología y Bioinformática Genómica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Lázaro Cárdenas, Mexico City 11340, Mexico; (M.A.L.-L.); (E.E.S.-P.); (J.C.P.-F.); (R.M.-R.)
| | - Alfonso Méndez-Tenorio
- Laboratorio de Biotecnología y Bioinformática Genómica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Lázaro Cárdenas, Mexico City 11340, Mexico; (M.A.L.-L.); (E.E.S.-P.); (J.C.P.-F.); (R.M.-R.)
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Giroux P, Palmer A, Thomas A, Camacho-Gomez SM. Helicobacter pylori Found Guilty of Obstructive Jaundice: A Pediatric Case Report. JPGN REPORTS 2023; 4:e348. [PMID: 38034451 PMCID: PMC10684119 DOI: 10.1097/pg9.0000000000000348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 06/15/2023] [Indexed: 12/02/2023]
Abstract
Pediatric Helicobacter pylori infection represents a small proportion of disease that is otherwise decreasing in the developed world. Typical presentations have been well-described in the literature. We report a 15-year-old male who presented with jaundice, anemia, dark urine, and poorly characterized abdominal pain and was found to have obstructive jaundice secondary to a duodenal ulcer resulting from H. pylori infection. Obstructive jaundice is a seldom reported complication of duodenal ulcer, particularly in children. This report reviews H. pylori infection, outlines complications of peptic ulcer disease, and illustrates the rarity of obstructive jaundice as a presenting sign of duodenal ulcer in children.
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Affiliation(s)
- Parker Giroux
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's of Mississippi, University of Mississippi Medical Center, Jackson, MS
| | - Andrew Palmer
- Department of Radiology, University of Mississippi Medical Center, Jackson, MS
| | - Aby Thomas
- Department of Radiology, University of Mississippi Medical Center, Jackson, MS
| | - Sandra Mabel Camacho-Gomez
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's of Mississippi, University of Mississippi Medical Center, Jackson, MS
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Gan Y, Zhao G, Wang Z, Zhang X, Wu MX, Lu M. Bacterial Membrane Vesicles: Physiological Roles, Infection Immunology, and Applications. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301357. [PMID: 37357142 PMCID: PMC10477901 DOI: 10.1002/advs.202301357] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/19/2023] [Indexed: 06/27/2023]
Abstract
Bacterial or fungal membrane vesicles, traditionally considered as microbial metabolic wastes, are secreted mainly from the outer membrane or cell membrane of microorganisms. However, recent studies have shown that these vesicles play essential roles in direct or indirect communications among microorganisms and between microorganisms and hosts. This review aims to provide an updated understanding of the physiological functions and emerging applications of bacterial membrane vesicles, with a focus on their biogenesis, mechanisms of adsorption and invasion into host cells, immune stimulatory effects, and roles in the much-concerned problem of bacterial resistance. Additionally, the potential applications of these vesicles as biomarkers, vaccine candidates, and drug delivery platforms are discussed.
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Affiliation(s)
- Yixiao Gan
- Department of Transfusion MedicineHuashan HospitalFudan UniversityShanghai200040P. R. China
| | - Gang Zhao
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200240P. R. China
| | - Zhicheng Wang
- Department of Transfusion MedicineHuashan HospitalFudan UniversityShanghai200040P. R. China
| | - Xingcai Zhang
- John A. Paulson School of Engineering and Applied SciencesHarvard UniversityCambridgeMA02138USA
| | - Mei X. Wu
- Wellman Center for PhotomedicineMassachusetts General HospitalDepartment of DermatologyHarvard Medical School, 50 Blossom StreetBostonMA02114USA
| | - Min Lu
- Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200240P. R. China
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Zhou WT, Dai YY, Liao LJ, Yang SX, Chen H, Huang L, Zhao JL, Huang YQ. Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation. World J Gastroenterol 2023; 29:4860-4872. [PMID: 37701137 PMCID: PMC10494766 DOI: 10.3748/wjg.v29.i32.4860] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/15/2023] [Accepted: 07/31/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study. AIM To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections. METHODS H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified. RESULTS Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes. CONCLUSION Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.
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Affiliation(s)
- Wen-Ting Zhou
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yuan-Yuan Dai
- School of Basic Medicine, Youjiang Medical University for Nationalities, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Li-Juan Liao
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Shi-Xian Yang
- Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Hao Chen
- School of Basic Medicine, Department of Pathology, Wannan Medical College, Wuhu 533000, Anhui Province, China
| | - Liang Huang
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Juan-Li Zhao
- School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yan-Qiang Huang
- School of Basic Sciences, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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12
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Elshenawi Y, Hu S, Hathroubi S. Biofilm of Helicobacter pylori: Life Cycle, Features, and Treatment Options. Antibiotics (Basel) 2023; 12:1260. [PMID: 37627679 PMCID: PMC10451559 DOI: 10.3390/antibiotics12081260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
Helicobacter pylori is a gastric pathogen that infects nearly half of the global population and is recognized as a group 1 carcinogen by the Word Health Organization. The global rise in antibiotic resistance has increased clinical challenges in treating H. pylori infections. Biofilm growth has been proposed to contribute to H. pylori's chronic colonization of the host stomach, treatment failures, and the eventual development of gastric diseases. Several components of H. pylori have been identified to promote biofilm growth, and several of these may also facilitate antibiotic tolerance, including the extracellular matrix, outer membrane proteins, shifted morphology, modulated metabolism, efflux pumps, and virulence factors. Recent developments in therapeutic approaches targeting H. pylori biofilm have shown that synthetic compounds, such as small molecule drugs and plant-derived compounds, are effective at eradicating H. pylori biofilms. These combined topics highlight the necessity for biofilm-based research in H. pylori, to improve current H. pylori-targeted therapeutic approaches and alleviate relative public health burden. In this review we discuss recent discoveries that have decoded the life cycle of H. pylori biofilms and current biofilm-targeted treatment strategies.
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Affiliation(s)
- Yasmine Elshenawi
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA;
| | - Shuai Hu
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064, USA;
| | - Skander Hathroubi
- Spartha Medical, CRBS 1 Rue Eugène Boeckel, 67000 Strasbourg, France
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13
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Doulberis M, Kountouras J, Stadler T, Meerwein C, Polyzos SA, Kulaksiz H, Chapman MH, Rogler G, Riva D, Linas I, Kavaliotis J, Kazakos E, Mouratidou M, Liatsos C, Papaefthymiou A. Association between Helicobacter pylori Infection and Nasal Polyps: A Systematic Review and Meta-Analysis. Microorganisms 2023; 11:1581. [PMID: 37375083 DOI: 10.3390/microorganisms11061581] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 05/20/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) has definite or possible associations with multiple local and distant manifestations. H. pylori has been isolated from multiple sites throughout the body, including the nose. Clinical non-randomized studies with H. pylori report discrepant data regarding the association between H. pylori infection and nasal polyps. The aim of this first systematic review and meta-analysis was the assessment of the strength of the association between H. pylori infection and incidence of nasal polyps. METHODS We performed an electronic search in the three major medical databases, namely PubMed, EMBASE and Cochrane, to extract and analyze data as per PRISMA guidelines. RESULTS Out of 57 articles, 12 studies were graded as good quality for analysis. Male-to-female ratio was 2:1, and age ranged between 17-78 years. The cumulative pooled rate of H. pylori infection in the nasal polyp group was 32.3% (controls 17.8%). The comparison between the two groups revealed a more significant incidence of H. pylori infection among the nasal polyp group (OR 4.12), though with high heterogeneity I2 = 66%. Subgroup analysis demonstrated that in European studies, the prevalence of H. pylori infection among the nasal polyp group was significantly higher than in controls, yielding null heterogeneity. Subgroup analysis based on immunohistochemistry resulted in null heterogeneity with preserving a statistically significant difference in H. pylori infection prevalence between the groups. CONCLUSION The present study revealed a positive association between H. pylori infection and nasal polyps.
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Affiliation(s)
- Michael Doulberis
- Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland
- Department of Gastroenterology, University Hospital Zurich, 8091 Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Macedonia, Greece
| | - Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Macedonia, Greece
| | - Thomas Stadler
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Christian Meerwein
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Macedonia, Greece
| | - Hasan Kulaksiz
- Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland
| | - Michael H Chapman
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London NW1 2BU, UK
| | - Gerhard Rogler
- Department of Gastroenterology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Daniele Riva
- Gastrocentro Plus, Private Gastroenterological Practice, 6900 Lugano, Switzerland
| | - Ioannis Linas
- Gastroenterologische Gruppenpraxis, Private Gastroenterological Practice, 3011 Bern, Switzerland
| | - John Kavaliotis
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Macedonia, Greece
- School of Healthcare Sciences, Midwifery Department, University of West Macedonia, 50100 Kozani, Macedonia, Greece
| | - Maria Mouratidou
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Macedonia, Greece
| | - Christos Liatsos
- Department of Gastroenterology, 401 General Military Hospital of Athens, 11525 Athens, Attica, Greece
| | - Apostolis Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London NW1 2BU, UK
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14
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Di Fermo P, Di Lodovico S, Di Campli E, D'Arcangelo S, Diban F, D'Ercole S, Di Giulio M, Cellini L. Helicobacter pylori Dormant States Are Affected by Vitamin C. Int J Mol Sci 2023; 24:ijms24065776. [PMID: 36982855 PMCID: PMC10057322 DOI: 10.3390/ijms24065776] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/14/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
Helicobacter pylori colonizes human gastric mucosa, overcoming stressful conditions and entering in a dormant state. This study evaluated: (i) H. pylori's physiological changes from active to viable-but-non-culturable (VBNC) and persister (AP) states, establishing times/conditions; (ii) the ability of vitamin C to interfere with dormancy generation/resuscitation. A dormant state was induced in clinical MDR H. pylori 10A/13 by: nutrient starvation (for VBNC generation), incubating in an unenriched medium (Brucella broth) or saline solution (SS), and (for AP generation) treatment with 10xMIC amoxicillin (AMX). The samples were monitored after 24, 48, and 72 h, 8-14 days by OD600, CFUs/mL, Live/Dead staining, and an MTT viability test. Afterwards, vitamin C was added to the H. pylori suspension before/after the generation of dormant states, and monitoring took place at 24, 48, and 72 h. The VBNC state was generated after 8 days in SS, and the AP state in AMX for 48 h. Vitamin C reduced its entry into a VBNC state. In AP cells, Vitamin C delayed entry, decreasing viable coccal cells and increasing bacillary/U-shaped bacteria. Vitamin C increased resuscitation (60%) in the VBNC state and reduced the aggregates of the AP state. Vitamin C reduced the incidence of dormant states, promoting the resuscitation rate. Pretreatment with Vitamin C could favor the selection of microbial vegetative forms that are more susceptible to H. pylori therapeutical schemes.
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Affiliation(s)
- Paola Di Fermo
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Silvia Di Lodovico
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Emanuela Di Campli
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Sara D'Arcangelo
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Firas Diban
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Simonetta D'Ercole
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Mara Di Giulio
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
| | - Luigina Cellini
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy
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15
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Shu C, Xu Z, He C, Xu X, Zhou Y, Cai B, Zhu Y. Application of biomaterials in the eradication of Helicobacter pylori: A bibliometric analysis and overview. Front Microbiol 2023; 14:1081271. [PMID: 37007524 PMCID: PMC10061102 DOI: 10.3389/fmicb.2023.1081271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Helicobacter pylori is a prominent cause of gastritis, peptic ulcer, and gastric cancer. It is naturally colonized on the surface of the mucus layer and mucosal epithelial cells of the gastric sinus, surrounded not only by mucus layer with high viscosity that prevents the contact of drug molecules with bacteria but also by multitudinous gastric acid and pepsin, inactivating the antibacterial drug. With high-performance biocompatibility and biological specificity, biomaterials emerge as promising prospects closely associated with H. pylori eradication recently. Aiming to thoroughly summarize the progressing research in this field, we have screened 101 publications from the web of science database and then a bibliometric investigation was performed on the research trends of the application of biomaterials in eradicating H. pylori over the last decade utilizing VOSviewer and CiteSpace to establish the relationship between the publications, countries, institutions, authors, and most relevant topics. Keyword analysis illustrates biomaterials including nanoparticles (NPs), metallic materials, liposomes, and polymers are employed most frequently. Depending on their constituent materials and characterized structures, biomaterials exhibit diverse prospects in eradicating H. pylori regarding extending drug delivery time, avoiding drug inactivation, target response, and addressing drug resistance. Furthermore, we overviewed the challenges and forthcoming research perspective of high-performance biomaterials in H. pylori eradication based on recent studies.
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Affiliation(s)
- Chunxi Shu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhou Xu
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Cong He
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yanan Zhou
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Baihui Cai
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- *Correspondence: Yin Zhu,
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Türkuçar S, Bülbül G, Ünsal E, Özer E, Erdağ TK, Erkoç E, Makay B. Exploring the immunological basis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: immunohistochemical staining features of palatine tonsils. Clin Rheumatol 2023:10.1007/s10067-023-06563-2. [PMID: 36892710 DOI: 10.1007/s10067-023-06563-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/09/2023] [Accepted: 02/24/2023] [Indexed: 03/10/2023]
Abstract
OBJECTIVES Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome during early childhood period with regular febrile attacks of sterile upper airway inflammation. The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily. The aim of this study is to explore the immunological basis of PFAPA by evaluating the cellular properties of tonsils, and microbial exposition such as Helicobacter pylori on tonsillectomy materials. METHODS The paraffinized tonsil samples of 26 PFAPA and 29 control patients with obstructive upper airway disorder were compared in terms of immunohistochemical staining features including CD4, CD8, CD123, CD1a, CD20, and H. pylori. RESULTS The median number of CD8+ cells was 1485 (1218-1287) in PFAPA while it was 1003 (852-1261.5) in control group and the difference was statistically significant (p=0.001). Similarly, CD4+ cell counts were statistically higher in PFAPA group than control (833.5 vs 622). The ratio of CD4/CD8 did not differ between two groups; also, there was no statistically difference in terms of the other immunohistochemical staining results, such as CD20, CD1a, CD123 and H. pylori. CONCLUSION This is the largest number of pediatric tonsillar tissue study of PFAPA patients in current literature and we emphasized the triggering effects of CD8+ and CD4+ T-cells on PFAPA tonsils. KEY POINTS • The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily. • In current study, 92.3% of our patients did not experience any attacks following operation similarly with literature. • We observed the increased number of CD4+ and CD8+ T cell counts on PFAPA tonsils compared to control group and emphasized the active role of both CD4+ and CD8+ cells localized on PFAPA tonsils in immune dysregulation. • Some other cell types evaluated in this study such as CD19+ (B cells), CD1a (dendritic cells), and CD123 (IL-3 receptors, for pluripotent stem cells) and H. pylori did not differ in PFAPA patients compared to the control group.
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Affiliation(s)
- Serkan Türkuçar
- Department of Pediatric Rheumatology, Dokuz Eylul University, Izmir, Turkey.
- Division of Pediatric Rheumatology, Konya City Hospital, Karatay/Konya, Turkey.
| | - Göksenil Bülbül
- Department of Medical Pathology, Dokuz Eylul University, Izmir, Turkey
| | - Erbil Ünsal
- Department of Pediatric Rheumatology, Dokuz Eylul University, Izmir, Turkey
| | - Erdener Özer
- Department of Medical Pathology, Dokuz Eylul University, Izmir, Turkey
| | - Taner Kemal Erdağ
- Department of Otorhinolaryngology, Dokuz Eylul University, Izmir, Turkey
| | - Erdal Erkoç
- Department of Otorhinolaryngology, Dokuz Eylul University, Izmir, Turkey
| | - Balahan Makay
- Department of Pediatric Rheumatology, Dokuz Eylul University, Izmir, Turkey
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17
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Chitas R, Nunes C, Reis S, Parreira P, Martins MCL. How Charge, Size and Protein Corona Modulate the Specific Activity of Nanostructured Lipid Carriers (NLC) against Helicobacter pylori. Pharmaceutics 2022; 14:2745. [PMID: 36559239 PMCID: PMC9785867 DOI: 10.3390/pharmaceutics14122745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/30/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022] Open
Abstract
The major risk factor associated with the development of gastric cancer is chronic infection with Helicobacter pylori. The available treatments, based on a cocktail of antibiotics, fail in up to 40% of patients and disrupt their gut microbiota. The potential of blank nanostructured lipid carriers (NLC) for H. pylori eradication was previously demonstrated by us. However, the effect of NLC charge, size and protein corona on H. pylori-specific bactericidal activity herein studied was unknown at that time. All developed NLC formulations proved bactericidal against H. pylori. Although cationic NLC had 10-fold higher bactericidal activity than anionic NLC, they lacked specificity, since Lactobacillus acidophilus was also affected. Anionic NLC achieved complete clearance in both H. pylori morphologies (rod- and coccoid-shape) by inducing alterations in bacteria membranes and the cytoplasm, as visualized by transmission electron microscopy (TEM). The presence of an NLC protein corona, composed of 93% albumin, was confirmed by mass spectrometry. This protein corona delayed the bactericidal activity of anionic NLC against H. pylori and hindered NLC activity against Escherichia coli. Overall, these results sustain the use of NLC as a promising antibiotic-free strategy targeting H. pylori.
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Affiliation(s)
- Rute Chitas
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
- ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
| | - Cláudia Nunes
- ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
- LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
| | - Salette Reis
- LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
| | - Paula Parreira
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
| | - Maria Cristina L. Martins
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
- ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
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18
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Zhong Z, Wang X, Li J, Zhang B, Yan L, Xu S, Chen G, Gao H. A study on the diagnosis of the Helicobacter pylori coccoid form with artificial intelligence technology. Front Microbiol 2022; 13:1008346. [PMID: 36386698 PMCID: PMC9651970 DOI: 10.3389/fmicb.2022.1008346] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 10/10/2022] [Indexed: 09/05/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) is an important pathogenic microorganism that causes gastric cancer, peptic ulcers and dyspepsia, and infects more than half of the world's population. Eradicating H. pylori is the most effective means to prevent and treat these diseases. H. pylori coccoid form (HPCF) causes refractory H. pylori infection and should be given more attention in infection management. However, manual HPCF recognition on slides is time-consuming and labor-intensive and depends on experienced pathologists; thus, HPCF diagnosis is rarely performed and often overlooked. Therefore, simple HPCF diagnostic methods need to be developed. Materials and methods We manually labeled 4,547 images from anonymized paraffin-embedded samples in the China Center for H. pylori Molecular Medicine (CCHpMM, Shanghai), followed by training and optimizing the Faster R-CNN and YOLO v5 models to identify HPCF. Mean average precision (mAP) was applied to evaluate and select the model. The artificial intelligence (AI) model interpretation results were compared with those of the pathologists with senior, intermediate, and junior experience levels, using the mean absolute error (MAE) of the coccoid rate as an evaluation metric. Results For the HPCF detection task, the YOLO v5 model was superior to the Faster R-CNN model (0.688 vs. 0.568, mean average precision, mAP); the optimized YOLO v5 model had a better performance (0.803 mAP). The MAE of the optimized YOLO v5 model (3.25 MAE) was superior to that of junior pathologists (4.14 MAE, p < 0.05), no worse than intermediate pathologists (3.40 MAE, p > 0.05), and equivalent to a senior pathologist (3.07 MAE, p > 0.05). Conclusion HPCF identification using AI has the advantage of high accuracy and efficiency with the potential to assist or replace pathologists in clinical practice for HPCF identification.
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Affiliation(s)
- Zishao Zhong
- School of Medicine, Institute of Digestive Disease, Tongji University, Shanghai, China
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xin Wang
- School of Medicine, Institute of Digestive Disease, Tongji University, Shanghai, China
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
- School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, China
| | - Jianmin Li
- Unicom Guangdong Industrial Internet Co., Ltd, Guangzhou, China
| | - Beiping Zhang
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lijuan Yan
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
| | - Shuchang Xu
- School of Medicine, Institute of Digestive Disease, Tongji University, Shanghai, China
- Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guangxia Chen
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, China
| | - Hengjun Gao
- School of Medicine, Institute of Digestive Disease, Tongji University, Shanghai, China
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
- Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- National Engineering Center for Biochips, Shanghai, China
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19
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Reshetnyak VI, Maev IV. Maintaining the metabolic homeostasis of Helicobacter pylori through chronic hyperglycemia in diabetes mellitus: A hypothesis. World J Meta-Anal 2022; 10:238-243. [DOI: 10.13105/wjma.v10.i5.238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/23/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection occurs in almost half of the world's population, most of whom are merely carriers of this microorganism. H. pylori is shown to be detected more frequently in patients with diabetes mellitus (DM) than in the general population, which is accompanied by a significantly increased risk of developing H. pylori-associated diseases. In addition, eradication therapy shows a low efficiency for H. pylori infection in patients with DM. There is a relationship between the level of chronic hyperglycemia and a higher detection rate of H. pylori as well as a lower efficiency of eradication therapy in patients with DM. The exact mechanisms of these phenomena are unknown. The authors make a hypothesis that explains the relationship between chronic hyperglycemia and the increased detection rate of H. pylori, as well as the mechanisms contributing to the improved survival of this bacterium in patients with DM during eradication therapy.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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20
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Kell DB, Pretorius E. The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications. Biochem J 2022; 479:1653-1708. [PMID: 36043493 PMCID: PMC9484810 DOI: 10.1042/bcj20220154] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 02/07/2023]
Abstract
Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
| | - Etheresia Pretorius
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
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21
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Dempsey E, Corr SC. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front Immunol 2022; 13:840245. [PMID: 35464397 PMCID: PMC9019120 DOI: 10.3389/fimmu.2022.840245] [Citation(s) in RCA: 184] [Impact Index Per Article: 61.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
In recent decades, probiotic bacteria have become increasingly popular as a result of mounting scientific evidence to indicate their beneficial role in modulating human health. Although there is strong evidence associating various Lactobacillus probiotics to various health benefits, further research is needed, in particular to determine the various mechanisms by which probiotics may exert these effects and indeed to gauge inter-individual value one can expect from consuming these products. One must take into consideration the differences in individual and combination strains, and conditions which create difficulty in making direct comparisons. The aim of this paper is to review the current understanding of the means by which Lactobacillus species stand to benefit our gastrointestinal health.
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Affiliation(s)
- Elaine Dempsey
- Trinity Biomedical Science Institute, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.,Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland
| | - Sinéad C Corr
- Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
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22
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Rosu OM, Gimiga N, Stefanescu G, Anton C, Paduraru G, Tataranu E, Balan GG, Diaconescu S. Helicobacter pylori Infection in a Pediatric Population from Romania: Risk Factors, Clinical and Endoscopic Features and Treatment Compliance. J Clin Med 2022; 11:2432. [PMID: 35566557 PMCID: PMC9099726 DOI: 10.3390/jcm11092432] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/17/2022] [Accepted: 04/22/2022] [Indexed: 12/18/2022] Open
Abstract
Background and Objectives: The aim of this study was to investigate the association between H. pylori positivity with specific symptoms, risk factors and endoscopic patterns among the pediatric population in northeastern Romania. Materials and Methods: A prospective study was performed in 18 months on 185 children aged 6−18 years with an indication for upper digestive endoscopy. Demographic, anamnestic, symptomatic, endoscopic and histologic data were recorded. Results: Of 116 H. pylori-positive children, the most affected group was 15−17 years. Most (65.5%) of them were girls, with a significant association (p < 0.001). The majority (66.4%) lived in a rural area and 47.4% of children had an unsafe source of water and lived in overcrowded houses with no basic sanitary comfort. The most frequent symptom was epigastric pain (56.9%), and the main endoscopic appearance was nodularity and hyperemia. Patients diagnosed with H. pylori started triple-therapy treatment for 14 days. Only 13.8% stopped the treatment, mainly because of a misunderstanding of the treatment protocol (9.5%). Conclusions: Romanian teen girls living in rural areas are at high risk for H. pylori infection. Epigastric pain and endoscopic nodularity of the gastric mucosa were associated with the infection. As the resistance of the bacteria is unknown in our country, future research is needed in order to improve the eradication rate.
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Affiliation(s)
- Oana-Maria Rosu
- Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu Str., 540139 Targu Mures, Romania;
- Clinical Department of Pediatric Gastroenterology, “St. Mary” Emergency Children’s Hospital, 700309 Iasi, Romania;
| | - Nicoleta Gimiga
- Clinical Department of Pediatric Gastroenterology, “St. Mary” Emergency Children’s Hospital, 700309 Iasi, Romania;
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; (C.A.); (G.G.B.)
| | - Gabriela Stefanescu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; (C.A.); (G.G.B.)
- Gastroenterology and Hepatology Institute, “St. Spiridon” Emergency Hospital, 1-3 Independetei Str., 700115 Iasi, Romania
| | - Carmen Anton
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; (C.A.); (G.G.B.)
- Gastroenterology and Hepatology Institute, “St. Spiridon” Emergency Hospital, 1-3 Independetei Str., 700115 Iasi, Romania
| | - Gabriela Paduraru
- Clinical Department of Pediatric Gastroenterology, “St. Mary” Emergency Children’s Hospital, 700309 Iasi, Romania;
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; (C.A.); (G.G.B.)
| | - Elena Tataranu
- Clinical Department of Pediatrics, Sf. Ioan cel Nou, Emergency Hospital, 720224 Suceava, Romania;
| | - Gheorghe G. Balan
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; (C.A.); (G.G.B.)
- Gastroenterology and Hepatology Institute, “St. Spiridon” Emergency Hospital, 1-3 Independetei Str., 700115 Iasi, Romania
| | - Smaranda Diaconescu
- Faculty of Medicine, “Titu Maiorescu” University of Medicine, 67A Gheorghe Petrascu Str., 031593 Bucharest, Romania;
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23
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Ejaz S, Ejaz S, Shahid R, Noor T, Shabbir S, Imran M. Chitosan-curcumin complexation to develop functionalized nanosystems with enhanced antimicrobial activity against hetero-resistant gastric pathogen. Int J Biol Macromol 2022; 204:540-554. [PMID: 35157901 DOI: 10.1016/j.ijbiomac.2022.02.039] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 02/01/2022] [Accepted: 02/08/2022] [Indexed: 12/13/2022]
Abstract
With the apparent stagnation in the antibiotic discovery and the propagation of multidrug resistance, Helicobacter pylori associated gastric infections are hard to eradicate. In pursuance of alternative medicines, in this study, covalent modification of chitosan (CS) polymer with curcumin (Cur) was accomplished. Proton Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy elucidated the covalent interaction between Cur and CS with characteristic peak of imine functional group (C=N). Scanning Electron Microscopy provided visual proof for surface topology, while size and zeta potential values further affirmed the development of curcumin functionalized chitosan nanosystems (Cur-FCNS). The complexation efficiency of CS with Cur was found as 70 ± 3% at an optimal ratio of 5:1 for CS and Cur, respectively. Cur-FCNS developed with ionic gelation and ultrasonication method demonstrated synergistic anti-H. pylori activity in growth-kinetics and anti-biofilm assays, which was superior to free Cur and even chitosan nanosystems. Under simulated gastric conditions, Cur-FCNS revealed cumulative-release of only 16 ± 0.8% till 40 h, which indicated its improved stability to interact with H. pylori. In silico findings affirmed high binding affinity of Cur-FCNS with multiple bacterial virulence factors. Thus, our results affirmed the exceptional potential of Cur-FCNS as next-generation alternative-medicine to treat resistant H. pylori.
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Affiliation(s)
- Sadaf Ejaz
- Department of Biosciences, Faculty of Sciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, Pakistan
| | - Saima Ejaz
- Research Centre for Modelling and Simulation (RCMS), National University of Science and Technology (NUST), Islamabad, Pakistan
| | - Ramla Shahid
- Department of Biosciences, Faculty of Sciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, Pakistan
| | - Tayyaba Noor
- School of Chemical and Materials Engineering (SCME), National University of Science and Technology (NUST), Islamabad, Pakistan
| | - Saima Shabbir
- Department of Materials Science and Engineering, Institute of Space Technology (IST), Islamabad 44000, Pakistan
| | - Muhammad Imran
- Department of Biosciences, Faculty of Sciences, COMSATS University Islamabad (CUI), Park Road, Islamabad, Pakistan.
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24
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Sharndama HC, Mba IE. Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms. Braz J Microbiol 2022; 53:33-50. [PMID: 34988937 PMCID: PMC8731681 DOI: 10.1007/s42770-021-00675-0] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.
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Affiliation(s)
| | - Ifeanyi Elibe Mba
- Department of Microbiology, University of Nigeria, Nsukka, Enugu, Nigeria.
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25
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Spiegel M, Krzyżek P, Dworniczek E, Adamski R, Sroka Z. In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori. MOLECULES (BASEL, SWITZERLAND) 2021; 27:molecules27010020. [PMID: 35011255 PMCID: PMC8746548 DOI: 10.3390/molecules27010020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/15/2021] [Accepted: 12/20/2021] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.
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Affiliation(s)
- Maciej Spiegel
- Department of Pharmacognosy and Herbal Medicines, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland;
- Correspondence: (M.S.); (P.K.)
| | - Paweł Krzyżek
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland;
- Correspondence: (M.S.); (P.K.)
| | - Ewa Dworniczek
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland;
| | - Ryszard Adamski
- Laboratory of Microscopic Techniques, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63, 50-001 Wroclaw, Poland;
| | - Zbigniew Sroka
- Department of Pharmacognosy and Herbal Medicines, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland;
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26
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Assessment of the prospect for the use of colloidal silver nanoparticles for inactivation of Helicobacter pylori. ACTA BIOMEDICA SCIENTIFICA 2021. [DOI: 10.29413/abs.2021-6.5.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background. The growth of antibiotic resistance of Helicobacter pylori, a microorganism significant in the development of gastrointestinal diseases and inflammatory periodontal diseases, makes us think about the search for new approaches to the eradication of the microorganism. One solution to this problem may be to develop immunobiological preparations based on microorganisms inactivated with colloidal silver nanoparticles (CSNPs).The aim. To evaluate the inactivating ability of colloidal silver nanoparticles in vitro and in vivo with respect to H. pylori to determine the possibility of their use in the development of a specific immunobiological preparation.Materials and methods. The study design consisted in sequential execution of the steps of synthesis of colloidal silver nanoparticles with an assessment of the conditionality of the prepared preparations; isolating and identifying pure H. pylori culture; inactivation of H. pylori by synthesized silver nanoparticles; evaluation of the result of H. pylori inactivation in vitro and in vivo.Results. The conditionality of the synthesized colloidal silver nanoparticles of size 30 ± 3 nm, obtained using a step-by-step technique, was estimated by electron microscopy. Testing the inactivating activity of CSNPs on H. pylori showed that their effect on the culture for 3 hours at a ratio of volumes of CSNPs and 1:1 culture leads to a gradual decrease in the concentration of the microorganism until its complete death and lack of growth on the fifth passage. During the evaluation of the effect of CSNPs on H. pylori, it was shown that the inactivated culture retains its cultural and tinctorial properties; alters morphological properties and biochemical activity; becomes more sensitive to antibiotics and L. acidophilus; ceases to establish in the body of mice with an immunosuppression condition.Conclusions. Proposed method of synthesis of silver nanoparticles with proven inactivating activity against H. pylori can become a stage of biotechnological process of development of vaccine preparation both on the basis of given microorganism and in complex with CSNPs possessing multilevel antimicrobial effect, antioxidant and immunomodulating activity.
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27
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Saeedi A, Cummings NJ, McLean D, Connerton IF, Connerton PL. Venatorbacter cucullus gen. nov sp. nov a novel bacterial predator. Sci Rep 2021; 11:21393. [PMID: 34725408 PMCID: PMC8560859 DOI: 10.1038/s41598-021-00865-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 10/13/2021] [Indexed: 11/09/2022] Open
Abstract
A novel Gram-stain negative, aerobic, halotolerant, motile, rod-shaped, predatory bacterium ASxL5T, was isolated from a bovine slurry tank in Nottinghamshire, UK using Campylobacter hyointestinalis as prey. Other Campylobacter species and members of the Enterobacteriaceae were subsequently found to serve as prey. Weak axenic growth on Brain Heart Infusion agar was achieved upon subculture without host cells. The optimal growth conditions were 37 °C, at pH 7. Transmission electron microscopy revealed some highly unusual morphological characteristics related to prey availability. Phylogenetic analyses using 16S rRNA gene sequences showed that the isolate was related to members of the Oceanospirillaceae family but could not be classified clearly as a member of any known genus. Whole genome sequencing of ASxL5T confirmed the relationship to members the Oceanospirillaceae. Database searches revealed that several ASxL5T share 16S rRNA gene sequences with several uncultured bacteria from marine, and terrestrial surface and subsurface water. We propose that strain ASxL5T represents a novel species in a new genus. We propose the name Venatorbacter cucullus gen. nov., sp. nov. with ASxL5T as the type strain.
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Affiliation(s)
- Ahmed Saeedi
- grid.4563.40000 0004 1936 8868Division of Microbiology, Brewing and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD UK
| | - Nicola J. Cummings
- grid.4563.40000 0004 1936 8868Division of Microbiology, Brewing and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD UK
| | - Denise McLean
- grid.4563.40000 0004 1936 8868Nanoscale and Microscale Research Centre, University of Nottingham, Nottingham, NG7 2RD UK
| | - Ian F. Connerton
- grid.4563.40000 0004 1936 8868Division of Microbiology, Brewing and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD UK
| | - Phillippa L. Connerton
- grid.4563.40000 0004 1936 8868Division of Microbiology, Brewing and Biotechnology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD UK
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Mehrotra T, Devi TB, Kumar S, Talukdar D, Karmakar SP, Kothidar A, Verma J, Kumari S, Alexander SM, Retnakumar RJ, Devadas K, Ray A, Mutreja A, Nair GB, Chattopadhyay S, Das B. Antimicrobial resistance and virulence in Helicobacter pylori: Genomic insights. Genomics 2021; 113:3951-3966. [PMID: 34619341 DOI: 10.1016/j.ygeno.2021.10.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 09/10/2021] [Accepted: 10/01/2021] [Indexed: 12/26/2022]
Abstract
Microbes evolve rapidly by modifying their genome through mutations or acquisition of genetic elements. Antimicrobial resistance in Helicobacter pylori is increasingly prevalent in India. However, limited information is available about the genome of resistant H. pylori isolated from India. Our pan- and core-genome based analyses of 54 Indian H. pylori strains revealed plasticity of its genome. H. pylori is highly heterogenous both in terms of the genomic content and DNA sequence homology of ARGs and virulence factors. We observed that the H. pylori strains are clustered according to their geographical locations. The presence of point mutations in the ARGs and absence of acquired genetic elements linked with ARGs suggest target modifications are the primary mechanism of its antibiotic resistance. The findings of the present study would help in better understanding the emergence of drug-resistant H. pylori and controlling gastric disorders by advancing clinical guidance on selected treatment regimens.
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Affiliation(s)
- Tanshi Mehrotra
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - T Barani Devi
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Shakti Kumar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Daizee Talukdar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Sonali Porey Karmakar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Akansha Kothidar
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Jyoti Verma
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Shashi Kumari
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Sneha Mary Alexander
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - R J Retnakumar
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India
| | - Animesh Ray
- Department of Medicine, All India Institute of Medical, Science, New Delhi, India
| | - Ankur Mutreja
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India; Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge CB20QQ, United Kingdom
| | - G Balakrish Nair
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India
| | - Santanu Chattopadhyay
- Microbiome Laboratory, Pathogen Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
| | - Bhabatosh Das
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India.
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Senchukova MA, Tomchuk O, Shurygina EI. Helicobacter pylori in gastric cancer: Features of infection and their correlations with long-term results of treatment. World J Gastroenterol 2021; 27:6290-6305. [PMID: 34712033 PMCID: PMC8515796 DOI: 10.3748/wjg.v27.i37.6290] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/21/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a spiral-shaped bacterium responsible for the development of chronic gastritis, gastric ulcer, gastric cancer (GC), and MALT-lymphoma of the stomach. H. pylori can be present in the gastric mucosa (GM) in both spiral and coccoid forms. However, it is not known whether the severity of GM contamination by various vegetative forms of H. pylori is associated with clinical and morphological characteristics and long-term results of GC treatment. AIM To establish the features of H. pylori infection in patients with GC and their correlations with clinical and morphological characteristics of diseases and long-term results of treatment. METHODS Of 109 patients with GC were included in a prospective cohort study. H. pylori in the GM and tumor was determined by rapid urease test and by immunohistochemically using the antibody to H. pylori. The results obtained were compared with the clinical and morphological characteristics and prognosis of GC. Statistical analysis was performed using the Statistica 10.0 software. RESULTS H. pylori was detected in the adjacent to the tumor GM in 84.5% of cases, of which a high degree of contamination was noted in 50.4% of the samples. Coccoid forms of H. pylori were detected in 93.4% of infected patients, and only coccoid-in 68.9%. It was found that a high degree of GM contamination by the coccoid forms of H. pylori was observed significantly more often in diffuse type of GC (P = 0.024), in poorly differentiated GC (P = 0.011), in stage T3-4 (P = 0.04) and in N1 (P = 0.011). In cases of moderate and marked concentrations of H. pylori in GM, a decrease in 10-year relapse free and overall survival from 55.6% to 26.3% was observed (P = 0.02 and P = 0.07, respectively). The relationship between the severity of the GM contamination by the spiral-shaped forms of H. pylori and the clinical and morphological characteristics and prognosis of GC was not revealed. CONCLUSION The data obtained indicates that H. pylori may be associated not only with induction but also with the progression of GC.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
| | - Olesya Tomchuk
- Department of Histology, Cytology, Embryology, Orenburg State Medical University, Orenburg 460000, Russia
| | - Elena I Shurygina
- Department of Pathology, Orenburg State Medical University, Orenburg 460000, Russia
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The Partial Role of KLF4 and KLF5 in Gastrointestinal Tumors. Gastroenterol Res Pract 2021; 2021:2425356. [PMID: 34367275 PMCID: PMC8337138 DOI: 10.1155/2021/2425356] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/08/2021] [Accepted: 07/12/2021] [Indexed: 12/11/2022] Open
Abstract
Background KLF4 and KLF5 are members of the KLF transcription factor family, which play an important role in many gastrointestinal tumors. To gain a deeper insight into its function and role, bioinformatics was used to analyze the function and role of KLF4 and KLF5 in gastrointestinal tumors. Methods Data were collected from several online databases. Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN database analysis, Kaplan-Meier Plotter analysis, LOGpc system, the Pathology Atlas, and the STRING website were used to analyze the data. We download relevant data from TCGA and then perform GO enrichment and KEGG enrichment analysis. The effects of KLF5 on gastric cancer cell proliferation were measured by CCK-8 assay. The effect of KLF5 on the expression of CyclinD1 and MMP9 was detected by Western blot. Results KLF4 and KLF5 were differentially expressed in normal and tumor tissues of the gastrointestinal tract, and their differential expression is related to several genes or pathways. KEGG analysis showed that KLF5 was coexpressed with endocytosis-related genes. KLF5 promotes the proliferation of gastric cancer cells and the expression of metastasis-related molecules. Conclusion KLF4 and KLF5 are of great significance for developing gastrointestinal tumors and can be used as therapeutic targets.
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Tasse J, Dieppois G, Peyrane F, Tesse N. Improving the ability of antimicrobial susceptibility tests to predict clinical outcome accurately: Adding metabolic evasion to the equation. Drug Discov Today 2021; 26:2182-2189. [PMID: 34119667 DOI: 10.1016/j.drudis.2021.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/09/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023]
Abstract
Antimicrobial susceptibility tests (AST) are based on the minimal inhibitory concentration (MIC), the method used worldwide to guide antimicrobial therapy. Despite its relevance in correctly predicting clinical outcome for most acute infections, this approach is misleading for multiple clinical cases in which pathogens do not grow rapidly, uniformly or with physical protection. This behaviour, named 'metabolic evasion' (ME), enables bacteria to survive antimicrobials. ME can result from different, and sometimes combined, bacterial mechanisms such as biofilms, intracellular growth, persisters or dormancy. We discuss how ME can influence the MIC-based probability of target attainment. We identify clinical cases in which this approach is undermined by ME and propose a new approach that takes ME into account in order to improve patient management and the evaluation of innovative drugs.
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Affiliation(s)
- Jason Tasse
- BTF-E Group, BEAM Alliance, Le Dorian Bât B1 C/O Da Volterra, 172 Rue de Charonne, 75011 Paris, France; Biofilm Pharma, 307 Avenue Jean Jaurès, 69007 Lyon, France
| | - Guennaëlle Dieppois
- BTF-E Group, BEAM Alliance, Le Dorian Bât B1 C/O Da Volterra, 172 Rue de Charonne, 75011 Paris, France; Debiopharm, Chemin Messidor 5-7, Case postale 5911, 1002 Lausanne, Switzerland
| | - Frédéric Peyrane
- BTF-E Group, BEAM Alliance, Le Dorian Bât B1 C/O Da Volterra, 172 Rue de Charonne, 75011 Paris, France
| | - Nicolas Tesse
- BTF-E Group, BEAM Alliance, Le Dorian Bât B1 C/O Da Volterra, 172 Rue de Charonne, 75011 Paris, France; Septeos, 12 Avenue de la Grande Armée, 75017 Paris, France.
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Sánchez-Alonzo K, Silva-Mieres F, Arellano-Arriagada L, Parra-Sepúlveda C, Bernasconi H, Smith CT, Campos VL, García-Cancino A. Nutrient Deficiency Promotes the Entry of Helicobacter pylori Cells into Candida Yeast Cells. BIOLOGY 2021; 10:426. [PMID: 34065788 PMCID: PMC8151769 DOI: 10.3390/biology10050426] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/02/2021] [Accepted: 05/04/2021] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori, a Gram-negative bacterium, has as a natural niche the human gastric epithelium. This pathogen has been reported to enter into Candida yeast cells; however, factors triggering this endosymbiotic relationship remain unknown. The aim of this work was to evaluate in vitro if variations in nutrient concentration in the cultured medium trigger the internalization of H. pylori within Candida cells. We used H. pylori-Candida co-cultures in Brucella broth supplemented with 1%, 5% or 20% fetal bovine serum or in saline solution. Intra-yeast bacteria-like bodies (BLBs) were observed using optical microscopy, while intra-yeast BLBs were identified as H. pylori using FISH and PCR techniques. Intra-yeast H. pylori (BLBs) viability was confirmed using the LIVE/DEAD BacLight Bacterial Viability kit. Intra-yeast H. pylori was present in all combinations of bacteria-yeast strains co-cultured. However, the percentages of yeast cells harboring bacteria (Y-BLBs) varied according to nutrient concentrations and also were strain-dependent. In conclusion, reduced nutrients stresses H. pylori, promoting its entry into Candida cells. The starvation of both H. pylori and Candida strains reduced the percentages of Y-BLBs, suggesting that starving yeast cells may be less capable of harboring stressed H. pylori cells. Moreover, the endosymbiotic relationship between H. pylori and Candida is dependent on the strains co-cultured.
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Affiliation(s)
- Kimberly Sánchez-Alonzo
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
| | - Fabiola Silva-Mieres
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
| | - Luciano Arellano-Arriagada
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
| | - Cristian Parra-Sepúlveda
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
| | | | - Carlos T. Smith
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
| | - Víctor L. Campos
- Laboratory of Environmental Microbiology, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4070386, Chile;
| | - Apolinaria García-Cancino
- Laboratory of Bacterial Pathogenicity, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepcion, Concepción 4070386, Chile; (K.S.-A.); (F.S.-M.); (L.A.-A.); (C.P.-S.); (C.T.S.)
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Mao X, Jakubovics NS, Bächle M, Buchalla W, Hiller KA, Maisch T, Hellwig E, Kirschneck C, Gessner A, Al-Ahmad A, Cieplik F. Colonization of Helicobacter pylori in the oral cavity - an endless controversy? Crit Rev Microbiol 2021; 47:612-629. [PMID: 33899666 DOI: 10.1080/1040841x.2021.1907740] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori is associated with chronic gastritis, gastric or duodenal ulcers, and gastric cancer. Since the oral cavity is the entry port and the first component of the gastrointestinal system, the oral cavity has been discussed as a potential reservoir of H. pylori. Accordingly, a potential oral-oral transmission route of H. pylori raises the question concerning whether close contact such as kissing or sharing a meal can cause the transmission of H. pylori. Therefore, this topic has been investigated in many studies, applying different techniques for detection of H. pylori from oral samples, i.e. molecular techniques, immunological or biochemical methods and traditional culture techniques. While molecular, immunological or biochemical methods usually yield high detection rates, there is no definitive evidence that H. pylori has ever been isolated from the oral cavity. The specificity of those methods may be limited due to potential cross-reactivity, especially with H. pylori-like microorganisms such as Campylobacter spp. Furthermore, the influence of gastroesophageal reflux has not been investigated so far. This review aims to summarize and critically discuss previous studies investigating the potential colonization of H. pylori in the oral cavity and suggest novel research directions for targeting this critical research question.
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Affiliation(s)
- Xiaojun Mao
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Nicholas S Jakubovics
- Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Maria Bächle
- Department of Prosthetic Dentistry, Faculty of Medicine, Center for Dental Medicine, University of Freiburg, Freiburg, Germany
| | - Wolfgang Buchalla
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Karl-Anton Hiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Tim Maisch
- Department of Dermatology, University Hospital Regensburg, Regensburg, Germany
| | - Elmar Hellwig
- Department of Operative Dentistry and Periodontology, Faculty of Medicine, Center for Dental Medicine, University of Freiburg, Freiburg, Germany
| | | | - André Gessner
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Ali Al-Ahmad
- Department of Operative Dentistry and Periodontology, Faculty of Medicine, Center for Dental Medicine, University of Freiburg, Freiburg, Germany
| | - Fabian Cieplik
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
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Antibiotics as a Stressing Factor Triggering the Harboring of Helicobacter pylori J99 within Candida albicans ATCC10231. Pathogens 2021; 10:pathogens10030382. [PMID: 33806815 PMCID: PMC8004595 DOI: 10.3390/pathogens10030382] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/12/2021] [Accepted: 03/16/2021] [Indexed: 12/18/2022] Open
Abstract
First-line treatment for Helicobacter pylori includes amoxicillin and clarithromycin or metronidazole plus a proton pump inhibitor. Treatment failure is associated with antibiotic resistance and possibly also with internalization of H. pylori into eukaryotic cells, such as yeasts. Factors triggering the entry of H. pylori into yeast are poorly understood. Therefore, the aim of this study was to evaluate whether clarithromycin or amoxicillin trigger the entry of H. pylori into C. albicans cells. METHODS H. pylori J99 and C. albicans ATCC 10231 were co-cultured in the presence of subinhibitory concentrations of amoxicillin and clarithromycin as stressors. Bacterial-bearing yeasts were observed by fresh examination. The viability of bacteria within yeasts was evaluated, confirming the entry of bacteria into Candida, amplifying, by PCR, the H. pylori16S rRNA gene in total yeast DNA. RESULTS Amoxicillin significantly increased the entry of H. pylori into C. albicans compared to the control. CONCLUSION the internalization of H. pylori into C. albicans in the presence of antibiotics is dependent on the type of antibiotic used, and it suggests that a therapy including amoxicillin may stimulate the entry of the bacterium into Candida, thus negatively affecting the success of the treatment.
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Reshetnyak VI, Burmistrov AI, Maev IV. Helicobacter pylori: Commensal, symbiont or pathogen? World J Gastroenterol 2021; 27:545-560. [PMID: 33642828 PMCID: PMC7901052 DOI: 10.3748/wjg.v27.i7.545] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/28/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
This review considers the data on Helicobacter pylori (H. pylori), which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal diseases. The majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis, peptic ulcer disease, and gastric cancer, as well as methods for its eradication. However, in recent years, there have been more and more studies which have suggested that H. pylori has a beneficial, or potentially positive, effect on the human body. The authors have attempted to objectively analyze the information accumulated in the literature on H. pylori. Some studies consider it as one of the recently identified human bacterial pathogens, and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal (commensal from French to English is a table companion) or even a symbiont. The presented data discussing the presence or absence of the effect of H. pylori on human health suggest that there is an apparent ambiguity of the problem. The re-assessment of the data available on H. pylori infection is important in order to answer the question of whether it is necessary to create a program of mass H. pylori eradication or to apply a more personalized approach to treating patients with H. pylori-associated gastrointestinal diseases and to perform eradication therapy.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Alexandr Igorevich Burmistrov
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Koroleva PI, Kuzikov AV, Masamrekh RA, Filimonov DA, Dmitriev AV, Zaviyalova MG, Rikova SM, Shich EV, Makhova AA, Bulko TV, Gilep AA, Shumyantseva VV. Modeling of Drug-Drug Interactions between Omeprazole and Erythromycin in the Cytochrome P450-Dependent System In vitro. BIOCHEMISTRY (MOSCOW), SUPPLEMENT SERIES B: BIOMEDICAL CHEMISTRY 2021; 15:62-70. [DOI: 10.1134/s1990750821010030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 04/29/2020] [Accepted: 05/18/2020] [Indexed: 01/03/2025]
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Clinical and laboratory importance of detecting Helicobacter pylori coccoid forms for the selection of treatment. GASTROENTEROLOGY REVIEW 2020; 15:294-300. [PMID: 33777268 PMCID: PMC7988834 DOI: 10.5114/pg.2020.101557] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 01/14/2020] [Indexed: 12/18/2022]
Abstract
Helicobacter pylori grows and multiplies in the gastrointestinal tract (GIT) in about half of the world’s population. The prevalence of diseases associated with this bacterium is steadily increasing, which makes it necessary to search for optimal therapy aimed at eradication of this bacterium. Such diseases, for example, include gastric ulcer (GU) and chronic gastritis (CG). Unfortunately, modern possibilities for eradication therapy do not always make it possible to cure patients, and relapses often occur if it is cured. Nowadays, a particular topical issue has arisen, which concerns the resistance of Helicobacter pylori to therapies, because the effectiveness of medication used in clinics decreases every year. One of the mechanisms favouring tolerance to antibiotics is the transformation into a different morphological form – coccoid. This form of the bacterium was discovered quite a long time ago. Nevertheless, the question of its importance in clinical practice remains open to this day. Modern studies are aimed at understanding the role of coccoid forms of H. pylori in the survival of the population of these bacteria and at clarifying their role in the pathogenesis of gastrointestinal diseases. It is not known whether it is necessary to evaluate the contamination of a given morphological form of a bacterium of the gastric mucosa in clinical practice and its influence on the development of diseases etc. This article presents an overview and analysis of modern ideas about H. pylori coccoid forms and answers to the main questions posed in the last 10 years regarding the study of coccoid forms. Additionally, our results present a comparison of expression of virulence factors in coccoid and spiral forms of H. pylori.
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A peptide of a type I toxin-antitoxin system induces Helicobacter pylori morphological transformation from spiral shape to coccoids. Proc Natl Acad Sci U S A 2020; 117:31398-31409. [PMID: 33229580 DOI: 10.1073/pnas.2016195117] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Toxin-antitoxin systems are found in many bacterial chromosomes and plasmids with roles ranging from plasmid stabilization to biofilm formation and persistence. In these systems, the expression/activity of the toxin is counteracted by an antitoxin, which, in type I systems, is an antisense RNA. While the regulatory mechanisms of these systems are mostly well defined, the toxins' biological activity and expression conditions are less understood. Here, these questions were investigated for a type I toxin-antitoxin system (AapA1-IsoA1) expressed from the chromosome of the human pathogen Helicobacter pylori We show that expression of the AapA1 toxin in H. pylori causes growth arrest associated with rapid morphological transformation from spiral-shaped bacteria to round coccoid cells. Coccoids are observed in patients and during in vitro growth as a response to different stress conditions. The AapA1 toxin, first molecular effector of coccoids to be identified, targets H. pylori inner membrane without disrupting it, as visualized by cryoelectron microscopy. The peptidoglycan composition of coccoids is modified with respect to spiral bacteria. No major changes in membrane potential or adenosine 5'-triphosphate (ATP) concentration result from AapA1 expression, suggesting coccoid viability. Single-cell live microscopy tracking the shape conversion suggests a possible association of this process with cell elongation/division interference. Oxidative stress induces coccoid formation and is associated with repression of the antitoxin promoter and enhanced processing of its transcript, leading to an imbalance in favor of AapA1 toxin expression. Our data support the hypothesis of viable coccoids with characteristics of dormant bacteria that might be important in H. pylori infections refractory to treatment.
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Resuscitation of the Helicobacter pylori Coccoid Forms by Resuscitation Promoter Factor Obtained from Micrococcus Luteus. Curr Microbiol 2020; 77:2093-2103. [PMID: 32504323 DOI: 10.1007/s00284-020-02043-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 05/20/2020] [Indexed: 02/07/2023]
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Koroleva PI, Kuzikov AV, Masamrekh RA, Filimonov DA, Dmitriev AV, Zaviyalova MG, Rikova SM, Shich EV, Makhova AA, Bulko TV, Gilep AA, Shumyantseva VV. [Modeling of drug-drug interactions between omeprazole and erythromycin with cytochrome P450 3A4 in vitro assay]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2020; 66:241-249. [PMID: 32588830 DOI: 10.18097/pbmc20206603241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In the present study the electrochemical system based on recombinant cytochrome P450 3A4 (CYP3A4) was used for the investigation of potential drug-drug interaction between medicinal preparations employed for Helicobacter pylori eradication therapy. Drug interactions were demonstrated in association of omeprazole as a proton pump inhibitor (PPI) and macrolide antibiotic erythromycin during cytochrome P450 3A4-mediated metabolism. It was shown that in the presence of omeprazole the rate of N-demethylase activity of CYP3A4 to erythromycin measured by means of product (formaldehyde) formation decreased. Mass-spectrometry analysis of omeprazole sulfone as a CYP3A4-mediated metabolite demonstrated the absence of erythromycin influence on CYP3A4-dependent omeprazole metabolism. This phenomenon may be explained by lower spectral dissociation constant of CYP3A4-omeprazole complex (Kd = 18±2 μM) than that of CYP3A4-erythromycin complex (Kd = 52 μM). Using the electrochemical model of electrochemically-driven drug metabolism it is possible to register CYP3A4-mediated catalytic conversion of certain drugs. In vitro experiments of potential CYP3A4-mediated drug-drug interactions are in accordance with in silico modeling with program PASS and PoSMNA descriptors in the case of omeprazole/erythromycin combinations.
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Affiliation(s)
- P I Koroleva
- Institute of Biomedical Chemistry, Moscow, Russia
| | - A V Kuzikov
- Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia
| | - R A Masamrekh
- Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia
| | | | - A V Dmitriev
- Institute of Biomedical Chemistry, Moscow, Russia
| | | | - S M Rikova
- Sechenov First Moscow Medical State University (Sechenov University), Moscow, Russia
| | - E V Shich
- Sechenov First Moscow Medical State University (Sechenov University), Moscow, Russia
| | - A A Makhova
- Sechenov First Moscow Medical State University (Sechenov University), Moscow, Russia
| | - T V Bulko
- Institute of Biomedical Chemistry, Moscow, Russia
| | - A A Gilep
- Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Minsk, Belarus
| | - V V Shumyantseva
- Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia
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Szymczak A, Ferenc S, Majewska J, Miernikiewicz P, Gnus J, Witkiewicz W, Dąbrowska K. Application of 16S rRNA gene sequencing in Helicobacter pylori detection. PeerJ 2020; 8:e9099. [PMID: 32440373 PMCID: PMC7229771 DOI: 10.7717/peerj.9099] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 04/09/2020] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori is one of the major stomach microbiome components, promoting development of inflammation and gastric cancer in humans. H. pylori has a unique ability to transform into a coccoidal form which is difficult to detect by many diagnostic methods, such as urease activity detection, and even histopathological examination. Here we present a comparison of three methods for H. pylori identification: histological assessment (with eosin, hematoxylin, and Giemsa staining), polymerase chain reaction (PCR) detection of urease (ureA specific primers), and detection by 16S rRNA gene sequencing. The study employed biopsies from the antral part of the stomach (N = 40). All samples were assessed histologically which revealed H. pylori in eight patients. Bacterial DNA isolated from the bioptates was used as a template for PCR reaction and 16S rRNA gene sequencing that revealed H. pylori in 13 and in 20 patients, respectively. Thus, 16S rRNA gene sequencing was the most sensitive method for detection of H. pylori in stomach biopsy samples.
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Affiliation(s)
- Aleksander Szymczak
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Stanisław Ferenc
- Regional Specialist Hospital in Wrocław, Research and Development Center, Wrocław, Poland
| | - Joanna Majewska
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Paulina Miernikiewicz
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Jan Gnus
- Medical Academy in Wroclaw, Wrocław, Poland
| | - Wojciech Witkiewicz
- Regional Specialist Hospital in Wrocław, Research and Development Center, Wrocław, Poland
| | - Krystyna Dąbrowska
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
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Liu A, Wang Y, Song Y, Du Y. Treatment with compound Lactobacillus acidophilus followed by a tetracycline- and furazolidone-containing quadruple regimen as a rescue therapy for Helicobacter pylori infection. Saudi J Gastroenterol 2020; 26:78-83. [PMID: 32295932 PMCID: PMC7279076 DOI: 10.4103/sjg.sjg_589_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND/AIM Treatment of Helicobacter pylori infections has become more difficult because of increasing antibiotic resistance. We assessed the efficacy and safety of treatment with probiotics followed by a tetracycline- and furazolidone-containing quadruple regimen as rescue treatment for H. pylori infection. PATIENTS AND METHODS This retrospective study examined patients with at least two H. pylori eradication failures. Patients were given a two-week compound Lactobacillus acidophilus (1 g t.i.d.), followed by a quadruple antibiotic regimen (esomeprazole [20 mg b.i.d.] + bismuth potassium citrate [220 mg b.i.d.] + tetracycline [750 mg b.i.d.] + furazolidone [100 mg b.i.d.]) for 10 days as rescue therapy. Eradication was evaluated using the[13]C-urea breath test at 4 weeks after the end of therapy, and side effects were recorded. RESULTS The records of 50 patients were examined. Four cases experienced treatment failure, and one case received replacement with metronidazole because of allergy to furazolidone. The eradication rate was 92.0% [95% confidence interval (CI): 84.0-98.0%) in intention-to-treat (ITT) analysis and 91.8% (95% CI: 83.7-98.0%) in per protocol (PP) analysis. Side effects (mainly dizziness, dry mouth, and skin rash) occurred in 10 patients, all of which resolved after cessation of antibiotics. CONCLUSIONS Patients who failed multiple attempts at H. pylori eradication may benefit from a treatment with probiotics followed by a tetracycline- and furazolidone-containing quadruple regimen.
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Affiliation(s)
- Airu Liu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China,Address for correspondence: Dr. Airu Liu, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai - 200433, China. E-mail:
Dr. Yiqi Du, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai - 200433, China. E-mail:
| | - Yuxin Wang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yingxiao Song
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China,Address for correspondence: Dr. Airu Liu, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai - 200433, China. E-mail:
Dr. Yiqi Du, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai - 200433, China. E-mail:
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Morales-Espinosa R, Delgado G, Serrano LR, Castillo E, Santiago CA, Hernández-Castro R, Gonzalez-Pedraza A, Mendez JL, Mundo-Gallardo LF, Manzo-Merino J, Ayala S, Cravioto A. High expression of Helicobacter pylori VapD in both the intracellular environment and biopsies from gastric patients with severity. PLoS One 2020; 15:e0230220. [PMID: 32163505 PMCID: PMC7067408 DOI: 10.1371/journal.pone.0230220] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/24/2020] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.
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Affiliation(s)
- Rosario Morales-Espinosa
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Gabriela Delgado
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Luis-Roberto Serrano
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Elizabeth Castillo
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Carlos A. Santiago
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | | | - Alberto Gonzalez-Pedraza
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Jose L. Mendez
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | | | | | - Sergio Ayala
- Cátedras CONACyT-Instituto Nacional de Cancerología, Mexico City, Mexico
| | - Alejandro Cravioto
- Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Bálint L, Tiszai A, Kozák G, Dóczi I, Szekeres V, Inczefi O, Ollé G, Helle K, Róka R, Rosztóczy A. Epidemiologic characteristics of Helicobacter pylori infection in southeast Hungary. World J Gastroenterol 2019; 25:6365-6372. [PMID: 31754296 PMCID: PMC6861848 DOI: 10.3748/wjg.v25.i42.6365] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/10/2019] [Accepted: 10/17/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori (H. pylori) infection in Western Europe.
AIM To obtain data regarding the prevalence of H. pylori in Csongrád and Békés Counties in Hungary, evaluate the differences in its prevalence between urban and rural areas, and establish factors associated with positive seroprevalence.
METHODS One-thousand and one healthy blood donors [male/female: 501/500, mean age: 40 (19–65) years] were enrolled in this study. Subjects were tested for H. pylori IgG antibody positivity via enzyme-linked immunosorbent assay. Subgroup analysis by age, gender, smoking habits, alcohol consumption, and urban vs non-urban residence was also performed.
RESULTS The overall seropositivity of H. pylori was 32%. It was higher in males (34.93% vs 29.2%, P = 0.0521) and in rural areas (36.2% vs 27.94%, P = 0.0051). Agricultural/industrial workers were more likely to be positive for infection than office workers (38.35% vs 30.11%, P = 0.0095) and rural subjects in Békés County than those in Csongrád County (43.36% vs 33.33%, P = 0.0015).
CONCLUSION Although the prevalence of H. pylori infection decreased in recent decades in Southeast Hungary, it remains high in middle-aged rural populations. Generally accepted risk factors for H. pylori positivity appeared to be valid for the studied population.
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Affiliation(s)
- Lenke Bálint
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - Andrea Tiszai
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - Gábor Kozák
- Department of Physiology, University of Szeged, Szeged 6720, Hungary
| | - Ilona Dóczi
- Department of Clinical Microbiology, University of Szeged, Szeged 6725, Hungary
| | | | - Orsolya Inczefi
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - Georgina Ollé
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - Krisztina Helle
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - Richárd Róka
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
| | - András Rosztóczy
- Division of Gastroenterology, First Department of Medicine, University of Szeged, Szeged 6720, Hungary
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Feng J, Guo J, Wang JP, Chai BF. MiR-32-5p aggravates intestinal epithelial cell injury in pediatric enteritis induced by Helicobacter pylori. World J Gastroenterol 2019; 25:6222-6237. [PMID: 31749593 PMCID: PMC6848013 DOI: 10.3748/wjg.v25.i41.6222] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 10/11/2019] [Accepted: 10/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems, including diarrhea, vomiting, and bellyache in children. Clinically, Helicobacter pylori (H. pylori) infection is one of the common factors to cause pediatric enteritis. It has been demonstrated that aberrant expression of microRNAs (miRNAs) is found in gastrointestinal diseases caused by H. pylori, and we discovered a significant increase of miR-32-5p in H. pylori-related pediatric enteritis. However, the exact role of miR-32-5p in it is still unknown. AIM To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H. pylori. METHODS MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction. The biological role of miR-32-5p in H. pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry. The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay. The downstream mechanism of miR-32-5p was explored by using molecular biology methods. RESULTS We found that miR-32-5p was overexpressed in serum of H. pylori-induced pediatric enteritis. Further investigation revealed that H. pylori infection promoted the death of intestinal epithelial cells, and increased miR-32-5p expression. Moreover, miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells. Further exploration revealed that SMAD family member 6 (SMAD6) was the direct target of miR-32-5p, and SMAD6 overexpression partially rescued cell damage induced by H. pylori. The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-β-activated kinase 1 (TAK1)-p38 activation under H. pylori infection. CONCLUSION Our work uncovered the crucial role of aberrant expression of miR-32-5p in H. pylori-related pediatric enteritis, and suggested that the TAK1-p38 pathway is involved in it.
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Affiliation(s)
- Jing Feng
- Institute of Loess Plateau, Shanxi University, Taiyuan 030006, Shanxi Province, China
- Department of Gastroenterology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
| | - Jian Guo
- Department of General Surgery, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
| | - Jun-Ping Wang
- Department of Gastroenterology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
| | - Bao-Feng Chai
- Institute of Loess Plateau, Shanxi University, Taiyuan 030006, Shanxi Province, China
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Sun Y, Zhang J. Helicobacter pylori recrudescence and its influencing factors. J Cell Mol Med 2019; 23:7919-7925. [PMID: 31536675 PMCID: PMC6850920 DOI: 10.1111/jcmm.14682] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 08/21/2019] [Accepted: 08/25/2019] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (H pylori) is known as one of the most common infectious pathogens, with high infection and recurrence rates worldwide. The prevalence of H pylori is up to 90% in developing countries, while the annual recurrence rate is much higher than that in developed countries. Recurrence can occur either by recrudescence or reinfection. Compared with reinfection, the time window for recrudescence is generally shorter, followed by the recurrence of H pylori–associated diseases in the short‐term. Many factors are involved in the H pylori reinfection, such as the prevalence of H pylori infection, living conditions and economic development, health conditions and so forth. Previous studies focused less on H pylori recrudescence. Therefore, the influencing factors for H pylori recrudescence needed further exploration. This study reviewed the recrudescence of H pylori infection and its influencing factors.
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Affiliation(s)
- Yan Sun
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.,Department of Gastroenterology, Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Jun Zhang
- Department of Gastroenterology, Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou, China
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Ierardi E, Losurdo G, Fortezza RFL, Principi M, Barone M, Leo AD. Optimizing proton pump inhibitors in Helicobacter pylori treatment: Old and new tricks to improve effectiveness. World J Gastroenterol 2019; 25:5097-5104. [PMID: 31558859 PMCID: PMC6747288 DOI: 10.3748/wjg.v25.i34.5097] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 07/26/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
The survival and replication cycle of Helicobacter pylori (H. pylori) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.
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Affiliation(s)
- Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Rosa Federica La Fortezza
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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Reshetnyak TM, Doroshkevich IA, Seredavkina NV, Nasonov EL, Maev IV, Reshetnyak VI. The Contribution of Drugs and Helicobacter pylori to Gastric Mucosa Changes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Int J Rheumatol 2019; 2019:9698086. [PMID: 31191660 PMCID: PMC6525898 DOI: 10.1155/2019/9698086] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 02/01/2019] [Accepted: 04/15/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The nature and rate of gastric mucosal (GM) damage in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) remain to be among the unsolved problems. OBJECTIVE To define the role of H. pylori and drugs in the development of GM damages in SLE and APS. METHODS A study was conducted on 85 patients with SLE and APS. All the patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucosa of the gastric body and antrum. The presence of H. pylori in the gastric biopsy specimens was determined using polymerase chain reaction. RESULTS Endoscopic examination revealed that the patients with SLE and APS on admission had the following GM changes: antral gastritis (82.4%), erosions (24.7%), hemorrhages (8.2%), and pangastritis (8.2%). SLE and APS patients showed no direct correlation between the found GM damages and the presence of H. pylori. The use of glucocorticoid, low-dose acetylsalicylic acid, nonsteroidal anti-inflammatory drug, and anticoagulant in SLE and APS patients is accompanied by GM damage. CONCLUSION There was no evidence of the role of H. pylori in GM damage in the SLE and APS patients. More frequent detection of H. pylori was observed in anticoagulants or low-dose acetylsalicylic acid users than in glucocorticoids and nonsteroidal anti-inflammatory drugs ones.
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Affiliation(s)
- Tatiana M. Reshetnyak
- Department of Vascular Rheumatology, VA Nasonova Research Institute of Rheumatology, Kashirskoe shosse, 34A, 115522, Moscow, Russia
- Department of Rheumatology, Russian Medical Academy of Postgraduate Education, Barrikadnaya str., 2/1, 125993, Moscow, Russia
| | - Irina A. Doroshkevich
- Municipal Outpatient Clinic No 36, Moscow Department of Health, Novomar'inskaya str., 2, 109652, Moscow, Russia
| | - Natalia V. Seredavkina
- Department of Vascular Rheumatology, VA Nasonova Research Institute of Rheumatology, Kashirskoe shosse, 34A, 115522, Moscow, Russia
| | - Evgeny L. Nasonov
- Department of Systemic Connective Tissue Diseases, VA Nasonova Research Institute of Rheumatology, Kashirskoe shosse, 34A, 115522, Moscow, Russia
| | - Igor V. Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Delegatskaya St., 20, p. 1, 127473, Moscow, Russia
| | - Vasiliy I. Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Delegatskaya St., 20, p. 1, 127473, Moscow, Russia
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Suicide journey of H. pylori through gastric carcinogenesis: the role of non-H. pylori microbiome and potential consequences for clinical practice. Eur J Clin Microbiol Infect Dis 2019; 38:1591-1597. [PMID: 31114971 DOI: 10.1007/s10096-019-03564-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 04/09/2019] [Indexed: 12/24/2022]
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50
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Kahwash S, Reinhard H, Jarad M, Ladd V. Coccoid Helicobacter pylori: An uncommon form of a common pathogen. IBNOSINA JOURNAL OF MEDICINE AND BIOMEDICAL SCIENCES 2019. [DOI: 10.4103/ijmbs.ijmbs_48_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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