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Nguyen TMN, Tran VH, Ha TMT. Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: a cross-sectional study in central Vietnam. Braz J Microbiol 2024; 55:1393-1404. [PMID: 38676790 PMCID: PMC11153385 DOI: 10.1007/s42770-024-01328-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 04/01/2024] [Indexed: 04/29/2024] Open
Abstract
Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.
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Affiliation(s)
- Thi Mai Ngan Nguyen
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, 6, Ngo Quyen Street, Hue City, 49100, Vietnam
| | - Van Huy Tran
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam
- Centre of Gastroenterology and Endoscopy, University of Medicine and Pharmacy Hospital, Hue University, Hue City, Vietnam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, 6, Ngo Quyen Street, Hue City, 49100, Vietnam.
- Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam.
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Gouda MA, Saied SA, Edrees A, Mostafa RG, Elfert A, Seleem AA, Shams A, Afify S. Effect of concurrent infection of Helicobacter pylori with Toxoplasma gondii infection on gastric pathology. BMC Infect Dis 2024; 24:408. [PMID: 38627630 PMCID: PMC11020820 DOI: 10.1186/s12879-024-09270-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 03/28/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Toxoplasma gondii (T. gondii) and Helicobacter pylori (H. pylori) are among the most prevalent foodborne parasitic and bacterial infections worldwide. However, the concurrent impact of coinfection on gastric pathology has yet to be studied in depth. The effect of coinfection generally either adds a synergetic or antagonistic impact; we aimed in the current work to assess the impact of T. gondii coinfection on the progression of H. pylori-associated gastric pathology and reporting H. pylori virulent strains. The study was conducted on 82 patients complaining of persistent gastrointestinal symptoms with failed treatment response and prone to endoscopy. They were subjected to stool examination to detect H. pylori antigen, serological screening for latent toxoplasmosis, endoscopy, histopathological examination, and molecular detection of H. pylori virulence strains in gastric biopsies. Out of the 82 patients, 62 patients were positive for H. pylori antigen in stool and 55 patients confirmed positivity by histopathology; out of them, 37 patients had isolated Vac As1 variants, 11 patients had combined Vac As1 and Cag A variants, and 7 patients had combined Vac As1, Cag A and VacAs2 variants. Patients with the combined two or three variances showed significantly deteriorated histopathological features than patients with a single Vac As1 variant (P < 0.05). Latent toxoplasmosis was positive among 35/82 patients. Combined H. pylori and Toxoplasma gondii infection had significantly marked inflammation than patients with isolated infection (P < 0.05). CONCLUSION Screening for toxoplasmosis among H. pylori-infected patients is recommended as it is considered a potential risk factor for gastric inflammation severity. H. pylori gastric inflammation may be heightened by Toxoplasma coinfection.
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Affiliation(s)
- Marwa A Gouda
- Clinical and Molecular Parasitology Department, National Liver Institute, Menoufia University, Shibin Elkom, Menoufia, Egypt
| | - Sara A Saied
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shibin Elkom, Menoufia, Egypt.
| | - Ahmed Edrees
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin Elkom, Menoufia, Egypt
| | - Rasha Galal Mostafa
- Department of Medical Microbiology, Faculty of Medicine, Menoufia University, Shibin Elkom, Menoufia, Egypt
| | - Ashraf Elfert
- Clinical Biochemistry and Molecular Diagnostics department, National Liver Institute, Menoufia University, Shibin Elkom, Menoufia, Egypt
| | - Aya Abdallah Seleem
- Zoonoses department, Faculty of Veterinary medicine, Cairo University, Cairo, Egypt
| | - Asmaa Shams
- Department of Pathology, Faculty of Medicine, Menoufia University, Shibin Elkom, Menoufia, Egypt
| | - Sameh Afify
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin Elkom, Menoufia, Egypt
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Bhattacharjee A, Sahoo OS, Sarkar A, Bhattacharya S, Chowdhury R, Kar S, Mukherjee O. Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity. Infection 2024; 52:345-384. [PMID: 38270780 DOI: 10.1007/s15010-023-02159-9] [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: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 01/26/2024]
Abstract
PURPOSE This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.
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Affiliation(s)
- Arghyadeep Bhattacharjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
- Department of Microbiology, Kingston College of Science, Beruanpukuria, Barasat, West Bengal, 700219, India
| | - Om Saswat Sahoo
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Ahana Sarkar
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Saurabh Bhattacharya
- Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, The Hebrew University of Jerusalem, P.O.B. 12272, 9112001, Jerusalem, Israel
| | - Rukhsana Chowdhury
- School of Biological Sciences, RKM Vivekananda Educational and Research Institute Narendrapur, Kolkata, India
| | - Samarjit Kar
- Department of Mathematics, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India
| | - Oindrilla Mukherjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, 713209, India.
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Al-Jumaily AY, Al-Haddad A, Al-Jubori SS. New strategies for Helicobacter pylori isolation and sequencing analysis for virulence genes contributing to its pathogenicity. Mol Biol Rep 2024; 51:95. [PMID: 38194007 DOI: 10.1007/s11033-023-09038-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 11/28/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND Helicobacter pylori is a fastidious pathogen that is required a complicated medium for growth. Invading epithelial cells of the stomach. H. pylori virulence factors are classified by function, acidic resistivity, adhesion, chemotaxis and motility, molecular mimicry, immunological invasion and modulation, and toxins formation such as cytotoxin-associated genes A (cagA) and vacuolating cytotoxin A (vacA). This study aims to determine a simple and innovative technique to isolate H. pylori from gastric biopsies and assess pathogenicity by virulence factor gene detection. METHODS A total of 200 patients who were suspected of having H. pylori infection had two antral gastric biopsies undertaken. A rapid urease test (RUT) was used for one, and Brain Heart Infusion broth (BHI) was used to cultivate the other. The molecular study included diagnostics utilizing the 16sRNA housekeeping gene along with the identification of the virulence factors genes (cagA, cagT, and vacA) and sequencing, RESULT: Of the 200 antral gastric biopsies collected, 135 were positive rapid urease tests, and 17 H. pylori isolates were successfully obtained from 135 biopsies. The 16SrRNA as a housekeeping gene is confirmed, and about 53%, 70.5%, and 82.3% of the 17 isolates show carrying cagA, cagT, and vacA genes, respectively. All peptic ulcer isolates have the cagA gene, while Gastroesophageal Reflux Disease (GERD) and non-peptic ulcer disease (NPUD) isolates show the lack of the cagA gene. All bacteria, which were isolated from peptic ulcer, nodular gastritis, and gastritis patients, have a vacA gene. CONCLUSION The effective method for isolating H. pylori is centrifuging the transport broth after 24 h of incubation. The cagA toxin causes peptic ulcer while vacA toxin induces several histopathological changes in the stomach. Three virulence genes were present in all peptic ulcer-causing bacteria, while only one or none were present in the GERD and NPUD biopsy isolates.
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Affiliation(s)
- Asma Yahya Al-Jumaily
- Department of Biology, College of Science, Mustansiriyah University, Baghdad, 10046, Iraq
| | - Ahmed Al-Haddad
- Department of Physics, College of Science, Mustansiriyah University, Baghdad, 10046, Iraq
| | - Sawsan Sajid Al-Jubori
- Branch of Biotechnology, Department of Biology, College of Science, Mustansiriyah University, POX 10244, Baghdad, Iraq.
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Al-Ouqaili MT, Hussein RA, Majeed YH, Al-Marzooq F. Study of vacuolating cytotoxin A (vacA) genotypes of ulcerogenic and non-ulcerogenic strains of Helicobacter pylori and its association with gastric disease. Saudi J Biol Sci 2023; 30:103867. [PMID: 38020230 PMCID: PMC10663908 DOI: 10.1016/j.sjbs.2023.103867] [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: 09/17/2023] [Revised: 10/24/2023] [Accepted: 11/02/2023] [Indexed: 12/01/2023] Open
Abstract
Globally, Helicobacter pylori (H. pylori), a stomach pathogen, is present in around 50 % of the population. This bacterial infection produces persistent inflammation, which significantly raises the risk of duodenal, gastric ulcer, and stomach cancer. The goal of this study is to identify the vacA genotypes in H. pylori and analyze how they relate to medical conditions brought on by the bacteria and clarithromycin resistance. PCR was used to describe 115 endoscopic stomach samples from infected patients and identify vacA gene. Of the 115 research participants, H. pylori was found in 81 (70.4 %) of them. Of the isolated cultures, only 38 (69.1 %) were resistant to clarithromycin. VacA was discovered in 55 (67.9 %) of the samples that had H. pylori in them. Patients with gastritis were more likely to have s2m2 strains of infection (66.7 %), while those with gastric and duodenal ulcers were more likely to have s1m1 strains (64.7 %). VacA-positive H. pylori strains (60 % n = 33) were more resistant to clarithromycin versus (19.2 % n = 5) for vacA-negative bacteria. Clarithromycin resistance was significantly linked to vacA s2m2 in H. pylori isolates (75.9 %). According to the study's results, the vacA variants s1m1 and s2m2 have a strong connection with the emergence of H. pylori infections that cause peptic ulcer disease in the population of Iraq. Genetic testing is essential in predicting both the course of treatment and the outcome of H. pylori disease.
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Affiliation(s)
- Mushtak T.S. Al-Ouqaili
- Department of Microbiology, College of Medicine, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
| | - Rawaa A. Hussein
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
| | - Yasin H. Majeed
- Department of Internal Medicine, College of Medicine, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
| | - Farah Al-Marzooq
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
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Bustos-Fraga S, Salinas-Pinta M, Vicuña-Almeida Y, de Oliveira RB, Baldeón-Rojas L. Prevalence of Helicobacter pylori genotypes: cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. A cross-sectional study in Quito-Ecuador. BMC Gastroenterol 2023; 23:197. [PMID: 37280541 DOI: 10.1186/s12876-023-02838-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/30/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND The most prevalent stomach infection in the world is caused by Helicobacter pylori (H. pylori). Several pathogenicity genes, including cagA, vacA, babA2, dupA, iceA, and oipA, are associated with an increased risk of gastrointestinal disease such as peptic ulcer and stomach cancer. This research aims to determine the prevalence of different H. pylori genotypes and correlate their risk in the development of gastrointestinal diseases in the Ecuadorian population. METHODS A cross-sectional research of 225 patients at the Calderón Hospital in Quito, Ecuador, was conducted. End point PCRs were run to determine the presence of 16S rRNA, cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, and oipA virulence genes. Chi-square test, odds ratios (OR) and 95% confidence intervals (CI) were utilized for the statistical analysis. RESULTS H. pylori infection was present in 62.7% of people. Peptic ulcers were seen in 22.2% and malignant lesions in 3.6% of patients. Genes oipA (93.6%), vacA (s1) (70.9%), and babA2 (70.2%) were the most prevalent. cagA/vacA (s1m1) and cagA/oipA (s1m1) combinations were found in 31.2% and 22.7% of the cases, respectively. Acute inflammation has a significant correlation with the genes cagA (OR = 4.96 95% CI: 1.1-22.41), babA2 (OR = 2.78 95% CI: 1.06-7.3), and the cagA/oipA combination (OR = 4.78, 95% CI: 1.06-21.62). Follicular hyperplasia was associated with iceA1 (OR = 3.13; 95% CI: 1.2-8.16), babA2 (OR = 2.56; 95% CI: 1.14-5.77), cagA (OR = 2.19; 95% CI: 1.06-4.52), and the cagA/oipA combination (OR = 2.32, 95% CI: 1.12-4.84). The vacA (m1) and vacA (s1m1) genes were associated with gastric intestinal metaplasia (OR = 2.71 95% CI: 1.17-6.29) (OR = 2.33 95% CI: 1.03-5.24). Finally, we showed that cagA/vacA (s1m1) gene combination increased the risk of duodenal ulcer development (OR = 2.89, 95% CI 1.10-7.58). CONCLUSION This study makes a significant contribution by offering genotypic information regarding H. pylori infection. The presence of several H. pylori genes was associated with the onset of gastrointestinal illness in the Ecuadorian population.
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Affiliation(s)
- Santiago Bustos-Fraga
- Departamento de Gastroenterología Clínica, Hospital General Docente de Calderón, Quito, Ecuador
- Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
| | - Marco Salinas-Pinta
- Instituto de Investigación en Biomedicina, Universidad Central del Ecuador, Quito, Ecuador.
| | | | | | - Lucy Baldeón-Rojas
- Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
- Instituto de Investigación en Biomedicina, Universidad Central del Ecuador, Quito, Ecuador
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Yamaoka Y, Saruuljavkhlan B, Alfaray RI, Linz B. Pathogenomics of Helicobacter pylori. Curr Top Microbiol Immunol 2023; 444:117-155. [PMID: 38231217 DOI: 10.1007/978-3-031-47331-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
The human stomach bacterium Helicobacter pylori, the causative agent of gastritis, ulcers and adenocarcinoma, possesses very high genetic diversity. H. pylori has been associated with anatomically modern humans since their origins over 100,000 years ago and has co-evolved with its human host ever since. Predominantly intrafamilial and local transmission, along with genetic isolation, genetic drift, and selection have facilitated the development of distinct bacterial populations that are characteristic for large geographical areas. H. pylori utilizes a large arsenal of virulence and colonization factors to mediate the interaction with its host. Those include various adhesins, the vacuolating cytotoxin VacA, urease, serine protease HtrA, the cytotoxin-associated genes pathogenicity island (cagPAI)-encoded type-IV secretion system and its effector protein CagA, all of which contribute to disease development. While many pathogenicity-related factors are present in all strains, some belong to the auxiliary genome and are associated with specific phylogeographic populations. H. pylori is naturally competent for DNA uptake and recombination, and its genome evolution is driven by extraordinarily high recombination and mutation rates that are by far exceeding those in other bacteria. Comparative genome analyses revealed that adaptation of H. pylori to individual hosts is associated with strong selection for particular protein variants that facilitate immune evasion, especially in surface-exposed and in secreted virulence factors. Recent studies identified single-nucleotide polymorphisms (SNPs) in H. pylori that are associated with the development of severe gastric disease, including gastric cancer. Here, we review the current knowledge about the pathogenomics of H. pylori.
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Affiliation(s)
- Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Batsaikhan Saruuljavkhlan
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu Oita, 879-5593, Japan
- Helicobacter pylori and Microbiota Study Group, Universitas Airlangga, Surabaya, 60286, East Java, Indonesia
| | - Bodo Linz
- Division of Microbiology, Department Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
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Prevalence of Helicobacter pylori Virulence Genes and Their Association with Chronic Gastritis in Beijing, China. Curr Microbiol 2022; 80:33. [PMID: 36482124 DOI: 10.1007/s00284-022-03135-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori is closely related to chronic gastritis. The aim of the study was to investigate the correlation between H. pylori virulence genes and chronic gastritis in order to determine the pathogenic role of H. pylori virulence genes in chronic gastritis. Gastric mucosal tissues were obtained from 142 patients with chronic gastritis at three Beijing hospitals. The presence of virulence genes was determined by polymerase chain reaction (PCR) from H. pylori DNA. Multilocus sequence typing (MLST) and a phylogenetic tree were performed to characterize the overall genetic diversity. 91 new sequence types were identified by MLST in this study, and all strains showed high genetic diversity. The H. pylori isolates were divided into three types: hspEAsia strains (61 strains), hpEurope strains (15 strains), and mixed strains (16 strains). Some virulence genes were found to be significantly different between strains. The highest positive rates were found for dupA in chronic atrophic gastritis (AG), iceA1 in chronic non-atrophic gastritis with erosions, and iceA2 in chronic non-atrophic gastritis. The presence of dupA was found to be inversely related to the risk of AG. The H. pylori strains display high genetic diversity. Some virulence genes were found to be significantly different between diseases. The detection of various virulence genes is critical for screening high-risk populations for precancerous lesions and for the early prevention and control of gastric cancer.
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Karbalaei M, Talebi Bezmin Abadi A, Keikha M. Clinical relevance of the cagA and vacA s1m1 status and antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis. BMC Infect Dis 2022; 22:573. [PMID: 35752757 PMCID: PMC9233856 DOI: 10.1186/s12879-022-07546-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 06/15/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply challenged in the last decade. The goal of this analysis was to identify the potential relevance between cagA and vacA genotypes with reported antibiotic resistance observed in clinical H. pylori isolates. METHODS This literature search was conducted in databases such as Clarivate analytics, PubMed, Scopus, EMBASE, DOAJ, and Google Scholar by April 2022, regardless of language restrictions and publication date. Quality of the included studies was assessed by the Newcastle-Ottawa scale. Statistical analysis of retrieved studies was fulfilled using Comprehensive Meta-Analysis software version 2.2. Following quality appraisal of eligible studies, potential association between the status of cagA and vacA genes with resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was measured using odds ratio with 95% confidence interval. We also used sensitivity analyses and meta-regression to eliminate the source of heterogeneity from the overall estimates. Publication bias was assessed using funnel plot, Egger's test, Begg's test with the trim and fill procedure to assess the presence and magnitude of publication bias in the included studies. RESULTS Our findings suggested that a significant relationship between cagA status and increase resistance to metronidazole (OR: 2.69; 95% CI: 1.24-5.83). In subgroup analysis, we found that in the Western population, infection with cagA-positive strains could be led to increase in the resistance to metronidazole (OR: 1.59; 95% CI: 0.78-3.21), amoxicillin (OR: 19.68; 95% CI: 2.74-141.18), and levofloxacin (OR: 11.33; 95% CI: 1.39-91.85). After implementation of trim and fill method, the adjusted OR was not significantly differed from original estimates which in turn represented our subgroup analysis was statistically robust. On the other hand, vacA genotypes usually reduce the antibiotic resistance of this bacterium, so that vacA s1m1 significantly reduces the resistance to metronidazole (OR: 0.41; 95% CI: 0.20-0.86). Surprisingly, resistance of vacA s2m2 strains to antibiotics was low, the reason may be due to the non-inflammatory properties of strains containing vacA s2m2. The meta-regression and sensitivity analyses successfully reduced the effect of heterogeneity from the overall estimates. In addition, although the pooled OR is reduced after trim and fill adjustment but results do not change the conclusion regarding vacA genotypes and antibiotic resistance. CONCLUSIONS According to our findings, it was clearly demonstrated that cagA-positive strains are resistance to metronidazole, especially in Western countries. In Western countries, vacA s1m1 increases resistance to amoxicillin and levofloxacin. Based on the present findings, the vacA s1m1 genotype significantly increases resistance to metronidazole, while the vacA s1m2 decreases resistance to clarithromycin and metronidazole. Resistance to antibiotics in less virulent (vacA s2m2) strains is statistically significant lower than others.
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Affiliation(s)
- Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Masoud Keikha
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Tran TT, Nguyen AT, Quach DT, Pham DTH, Cao NM, Nguyen UTH, Dang ANT, Tran MA, Quach LH, Tran KT, Le NQ, Ung VV, Vo MNQ, Nguyen DT, Ngo KD, Tran TL, Nguyen VT. Emergence of amoxicillin resistance and identification of novel mutations of the pbp1A gene in Helicobacter pylori in Vietnam. BMC Microbiol 2022; 22:41. [PMID: 35114945 PMCID: PMC8812189 DOI: 10.1186/s12866-022-02463-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 01/31/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Amoxicillin-resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients. MATERIALS AND METHODS Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbor-joining tree building method. RESULTS There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 μg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310-596, with the proportion varying from 0.4 to 100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (AmoxS) and amoxicillin-resistant (AmoxR) samples, including Phe366 to Leu (p < 0.001), Ser414 to Arg (p < 0.001), Glu/Asn464-465 (p = 0.009), Val469 to Met (p = 0.021), Phe473 to Val (p < 0.001), Asp479 to Glu (p = 0.044), and Ser/Ala/Gly595-596 (p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A. CONCLUSIONS We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.
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Affiliation(s)
- Trung Thien Tran
- Department of Surgery, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Anh Tuan Nguyen
- Molecular Biomedical Center, University Medical Center, Ho Chi Minh City, Vietnam.
| | - Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Dao Thi-Hong Pham
- Department of Genetics, University of Science, Vietnam National University Ho Chi Minh, Ho Chi Minh City, Vietnam
| | - Nga Minh Cao
- Department of Microbiology-Parasitology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Uyen Thi-Hong Nguyen
- Department of Genetics, University of Science, Vietnam National University Ho Chi Minh, Ho Chi Minh City, Vietnam
| | - An Nguyen-Thanh Dang
- Department of Genetics, University of Science, Vietnam National University Ho Chi Minh, Ho Chi Minh City, Vietnam
| | - Minh Anh Tran
- Department of Surgery, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Loc Huu Quach
- University Medical Center - Campus 2, Ho Chi Minh City, Vietnam
| | | | - Nhan Quang Le
- Department of Endoscopy, University Medical Center, Ho Chi Minh City, Vietnam
| | - Viet Van Ung
- Department of Endoscopy, University Medical Center, Ho Chi Minh City, Vietnam
| | - Minh Ngoc-Quoc Vo
- Department of Endoscopy, University Medical Center, Ho Chi Minh City, Vietnam
| | - Danh Thanh Nguyen
- Molecular Biomedical Center, University Medical Center, Ho Chi Minh City, Vietnam
| | - Kha Dong Ngo
- Molecular Biomedical Center, University Medical Center, Ho Chi Minh City, Vietnam
| | - Trung Le Tran
- Department of Oral Biology, Yonsei University College of Density, Seoul, South Korea
| | - Vy Thuy Nguyen
- Department of Genetics, University of Science, Vietnam National University Ho Chi Minh, Ho Chi Minh City, Vietnam
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11
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Akbari S, Rezaeian T, Mohammadzadeh R, Meshkat Z, Namdar AB, Aryan E, Youssefi M, Pishdadian A, Ahmadi A, Farsiani H. Investigation of association between iceA, babA2, and oipA genotypes of Helicobacter pylori and IL-8-251 T>A polymorphism with clinical outcomes in Helicobacter pylori-infected Iranian patients. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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12
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Genotyping of Helicobacter pylori Virulence Genes cagA and vacA: Regional and National Study. Int J Microbiol 2021; 2021:5540560. [PMID: 34306090 PMCID: PMC8263242 DOI: 10.1155/2021/5540560] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 05/21/2021] [Accepted: 06/10/2021] [Indexed: 12/28/2022] Open
Abstract
Helicobacter pylori (H. pylori) plays a crucial role in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The presence of pathogenicity islands (PAI) genes contributes to the pathogenesis of many gastrointestinal disorders. Cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene (vacA) are the most known virulence genes in H. pylori. So, our aim was to study H. pylori virulence genes' role in gastric disorders pathogenesis. Our study included 150 adult patients who suffered dyspeptic symptoms and were referred to the GIT endoscopy unit. Gastric biopsies were attained for rapid urease test (RUT) and histopathological examination, and multiplex PCR technique for detection of virulence genes was performed. It was found that 100 specimens were (RUT) positive, of which sixty samples (60%) were PCR positive for H. pylori ureC gene. The vacA and cagA genes were identified in 61.6% and 53% of H. pylori strains, respectively. Only 5 cases were vacA-positive and cagA-negative. The most virulent vacA s1 allele existed in 56.6% of cases. Out of the 60 H. pylori strains, 66% had at least one virulence gene and 34% did not show any virulence gene. H. pylori infection showed significant increase with age. H. pylori are prevalent amid dyspeptic patients in our region. The main genotype combinations were vacA+/cagA+ of s1m1 genotype and they were frequently associated with peptic ulcer diseases, gastritis, and gastroesophageal reflux disease.
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13
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de Brito BB, Lemos FFB, Carneiro CDM, Viana AS, Barreto NMPV, Assis GADS, Braga BDC, Santos MLC, Silva FAFD, Marques HS, Silva NOE, de Melo FF. Immune response to Helicobacter pylori infection and gastric cancer development. World J Meta-Anal 2021; 9:257-276. [DOI: 10.13105/wjma.v9.i3.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
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Shetty V, Lingadakai R, Pai GC, Ballal M. Profile of Helicobacter pylori cagA &vacA genotypes and its association with the spectrum of gastroduodenal disease. Indian J Med Microbiol 2021; 39:495-499. [PMID: 34172322 DOI: 10.1016/j.ijmmb.2021.06.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 06/01/2021] [Accepted: 06/02/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE Globally, H. pylori virulence factors cagA and vacA genotypes and its variation is leading to the austere form of the gastroduodenal disease. Our objectives were to detect H. pylori in dyspeptic patients from biopsy samples with the validation of the various existing diagnostic tools and to screen the cagA, vacA genotypes profile from biopsy specimens and how it impacts in progression of gastroduodenal disease in southern India. METHODS 374 patients who attended endoscopy unit at Kasturba Hospital, Manipal with their consent obtained their biopsies. H. pylori were detected by HPE, Culture, RUT and PCR and its virulence gene were patterned with PCR. RESULTS The positive rate of H. pylori by HPE, RUT, Culture and PCR were 51.33%, 47.1%, 32.4% and 50.3% respectively and comparison by Bayesian LCMs analysis showed PCR is superior among them. The frequency of H. pylori virulence gene viz cagPAI (cagA) were 80.9%, and vacA alleles-s1m1 (42%), s1m2 (33%) and s2m2 (25%) genotypes by PCR respectively. Four combinations of cagA/vacA genotypes were noted, majority of strains harboured cagA+/vacA s1m1 genotypes (42.6%), interestingly this hyper-virulent strain more frequently seen in severe gastroduodenal disease whereas cagPAI negative strains as well as cagA-/vacA s2m2 combinations (19.1%) are seen most commonly in functional dyspepsia cases and depicted significant association by Chi-square test. CONCLUSIONS This study validates and compares the existing diagnostic methods for detecting H. pylori in biopsies. Also, it reveals some pattern of virulence gene combination will play a vital role in disease progression.
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Affiliation(s)
- Vignesh Shetty
- Enteric Diseases Division, Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, University of Cambridge, Cambridge, UK
| | - Ramachandra Lingadakai
- Department of Surgery, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Ganesh C Pai
- Department of Gastroenterology & Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Mamatha Ballal
- Enteric Diseases Division, Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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15
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Li Y, Lin R, Jin Y, Jin S, Chen B, Wu X. Genotyping Helicobacter pylori antibiotic resistance - and virulence-associated genes in patients with gastric cancer in Wenzhou, China. Arab J Gastroenterol 2021; 22:267-271. [PMID: 34120851 DOI: 10.1016/j.ajg.2021.05.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/02/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS Helicobacter pylori infection affects approximately 50% of the global population and has become a serious health concern related to gastric cancer, gastritis, and peptic ulcers. This organism acquires drug resistance through gene mutations, and its increasing resistance to antibiotics has severely influenced the effectiveness of eradication efforts. Therefore, we designed this study to determine the prevalence of H. pylori virulence- (cagA and vacA) and antibiotic resistance - associated genotypes in patients with gastric cancer infected with H. pylori in Whenzhou, China. PATIENTS AND METHODS We used polymerase chain reaction (PCR) to confirm H. pylori in cancerous and paracancerous tissue specimens from 225 patients. Then we tested the prevalence of virulence- and antibiotic resistance - associated genotypes in H. pylori using a PCR-based DNA-sequencing assay. RESULTS We observed H. pylori DNA in 222 of the 225 patients and found the most prevalent virulence-associated genotypes in cagA+ (97.75%) and vacAs1m1 (93.25%). Metronidazole resistance - associated gene mutation was G616A in rdxA; levofloxacin resistance - associated gene mutations were N87K, N87I, and D91G in gyrA; clarithromycin resistance - associated gene mutations were A2143G and A2142G in 23SrRNA; and amoxicillin resistance - associated gene mutation was T556S in pbp1. The most prevalent mutation related to antibiotic resistance was present in rdxA (97.30%), followed by gyrA (41.44%) and 23SrRNA (16.67%); the least prevalent was in pbp1 (2.25%). We observed single-gene mutations in 102 patients (45.95%) and found mutations in multiple genes (≥2 genes) in 116 patients (52.25%). CONCLUSION Patients with gastric cancer in Wenzhou, China, have high incidence infection caused by H. pylori with high-toxicity virulence genotypes. The frequency of gene mutations associated with metronidazole, levofloxacin, and clarithromycin resistances was high and that associated with amoxicillin resistance was relatively low. The mutation patterns were diverse, and the rates of multiple gene mutations were high.
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Affiliation(s)
- Yonglin Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Rixu Lin
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yin Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shuqing Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Bicheng Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Xiuling Wu
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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16
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Farsimadan M, Heravi FS, Emamvirdizadeh A, Moradi S, Iranpour H, Tabasi E, Eskandarion MR, Azizian R, Tabasi M. Evaluation of Helicobacter pylori Genotypes in Obese Patients with Gastric Ulcer, Duodenal Ulcer, and Gastric Cancer: An Observational Study. Dig Dis 2021; 40:355-361. [PMID: 34010829 DOI: 10.1159/000517262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/14/2021] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Obesity is a well-known risk factor for a variety of gastrointestinal disorders (GID). Helicobacter pylori is associated with different GID, such as gastric cancer and chronic gastritis. In this study, we investigated the prevalence of dominant genotypes in H. pylori isolated from obese patients diagnosed with gastric ulcer, duodenal ulcer, and gastric cancer. METHODS A total of 222 H. pylori-positive samples were collected from patients with obesity. GID and gastric cancer were identified by endoscopy and histopathology, respectively. Three biopsy specimens from the gastric antrum were obtained from each patient for culture tests, histological examination, and identification of vacuolating cytotoxin A (vacA) (vacA s1, vacA s2, vacA m1, vacA m2, vacA s1m1 vacA s1m2, vacA s2m1, and vacA s2m2), cagA, cagE, iceA1, oipA, dupA, and babA2 using polymerase chain reaction. RESULTS vacA, cagE, cagA, iceA1, oipA, dupA, and babA2 genes were detected in 222 (100%), 171 (77%), 161 (72.5%), 77 (34.6%), 77 (34.6%), 137 (61%), and 69 (31%) patients with obesity, respectively. Our findings revealed that vacA, iceA1, oipA, and babA2 were significantly associated with a higher risk of GID, while cagE, cagA, and dupA indicated no correlation with the development of GID. Also, in the combination of s- and m-region genotypes, s1m2 (79%) was the most frequently identified genotype in patients with obesity. A significant association was also found between cagA and the presence of vacA genotypes (except for vacA m1 and babA2). CONCLUSIONS This study indicated the high prevalence of different virulence genes in H. pylori isolated from obese patients and supported the significant role of H. pylori in the development of GID.
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Affiliation(s)
- Marziye Farsimadan
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | | | - Alireza Emamvirdizadeh
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Samaneh Moradi
- Department of Biology, Shahrood Branch, Islamic Azad University, Shahrood, Iran
| | - Hamidreza Iranpour
- Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran.,Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran
| | - Ehsan Tabasi
- Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Mohammad Reza Eskandarion
- Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.,Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Azizian
- Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Tabasi
- Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.,Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
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Alavifard H, Mirzaei N, Yadegar A, Baghaei K, Smith SM, Sadeghi A, Zali MR. Investigation of Clarithromycin Resistance-Associated Mutations and Virulence Genotypes of Helicobacter pylori Isolated from Iranian Population: A Cross-Sectional Study. Curr Microbiol 2021; 78:244-254. [PMID: 33251569 DOI: 10.1007/s00284-020-02295-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 11/11/2020] [Indexed: 12/17/2022]
Abstract
Antibiotic resistance has brought into question the efficiency of clarithromycin which is a vital component of eradication therapy for Helicobacter pylori infection. The point mutations within the 23S rRNA sequence of H. pylori isolates which contribute to clarithromycin resistance have yet to be fully characterized. This study was aimed to detect clarithromycin resistance-associated mutations and assess the prevalence of key virulence factors of H. pylori among Iranian patients. Amplification of 16S rRNA and glmM genes were done to identify H. pylori. Minimal inhibitory concentration (MIC) of clarithromycin in 82 H. pylori clinical isolates was determined by agar dilution method. Subsequently, various virulence markers including cagA, vacA, sabA, babA, and dupA of H. pylori were identified by PCR. PCR-sequencing was applied to detect point mutations in the 23S rRNA gene. Based on MIC values, 43.9% of H. pylori isolates showed resistance to clarithromycin. The babA and cagA genes were detected in 92.7% and 82.9% of isolates, assigned to be higher than other virulence factors. No significant relationship was found between the H. pylori virulence genotypes and clarithromycin susceptibility (P > 0.05). Analyzing the 23S rRNA sequences revealed A2143G (4/48, 8.3%) and A2142G (3/48, 6.2%) as the most prevalent mutations in clarithromycin-resistant isolates. Additionally, several novel mutations including G2220T, C2248T, A2624C, G2287A, T2188C, G2710C, C2248T, G2269A, and G2224T were also detected among either resistant or susceptible isolates. Our findings revealed the presence of several point mutations in the 23S rRNA gene of H. pylori isolates which may be associated with resistance to clarithromycin.
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Affiliation(s)
- Helia Alavifard
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasrin Mirzaei
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Kaveh Baghaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sinéad Marian Smith
- School of Medicine & School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, Maciejewski R. Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells 2020; 10:27. [PMID: 33375694 PMCID: PMC7824444 DOI: 10.3390/cells10010027] [Citation(s) in RCA: 198] [Impact Index Per Article: 39.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.
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Affiliation(s)
- Jacek Baj
- Department of Anatomy, Medical University of Lublin, 20-400 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, Piazza G. Cesare 11, 70124 Bari, Italy;
| | - Danuta Krasowska
- Department of Dermatology, Venerology and Paediatric Dermatology of Medical University of Lublin, 20-081 Lublin, Poland;
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Sukri A, Hanafiah A, Mohamad Zin N, Kosai NR. Epidemiology and role of Helicobacter pylori virulence factors in gastric cancer carcinogenesis. APMIS 2020; 128:150-161. [PMID: 32352605 DOI: 10.1111/apm.13034] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 02/09/2020] [Indexed: 02/06/2023]
Abstract
Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.
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Affiliation(s)
- Asif Sukri
- Programme of Biomedical Science, Faculty of Health Science, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Alfizah Hanafiah
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Noraziah Mohamad Zin
- Programme of Biomedical Science, Faculty of Health Science, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nik Ritza Kosai
- Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Hanafiah A, Lopes BS. Genetic diversity and virulence characteristics of Helicobacter pylori isolates in different human ethnic groups. INFECTION GENETICS AND EVOLUTION 2019; 78:104135. [PMID: 31837482 DOI: 10.1016/j.meegid.2019.104135] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 12/03/2019] [Accepted: 12/06/2019] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori is the most predominant bacterium in almost 50% of the world's population and colonization causes a persistent inflammatory response leading to chronic gastritis. It shows high genetic diversity and individuals generally harbour a distinct bacterial population. With the advancement of whole-genome sequencing technology, new H. pylori subpopulations have been identified that show admixture between various H. pylori strains. Genotypic variation of H. pylori may be related to the presence of virulence factors among strains and is associated with different outcomes of infection in different individuals. This review summarizes the genetic diversity in H. pylori strain populations and its virulence characteristics responsible for variable outcomes in different ethnic groups.
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Affiliation(s)
- Alfizah Hanafiah
- Department of Medical Microbiology & Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Bruno S Lopes
- Department of Medical Microbiology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, 0:025 Polwarth Building, Aberdeen AB25 2ZD, United Kingdom.
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Idowu A, Mzukwa A, Harrison U, Palamides P, Haas R, Mbao M, Mamdoo R, Bolon J, Jolaiya T, Smith S, Ally R, Clarke A, Njom H. Detection of Helicobacter pylori and its virulence genes (cagA, dupA, and vacA) among patients with gastroduodenal diseases in Chris Hani Baragwanath Academic Hospital, South Africa. BMC Gastroenterol 2019; 19:73. [PMID: 31088381 PMCID: PMC6518451 DOI: 10.1186/s12876-019-0986-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 04/11/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The global prevalence of H. pylori approaches 50%, with prevalence rates between 20 and 40% in developed countries and up to 90% in Africa and other developing nations of the world. Development of H. pylori-associated diseases is determined by a number of virulence factors. This study aimed at determining the prevalence of H. pylori infections and virulence genes (cagA, dupA, and vacA); the relationship between virulence factors and gastroduodenal diseases among patients. METHODS Gastric biopsies were obtained from patients and cultured, DNA was extracted from cultured isolates and biopsies for PCR assay after which samples were investigated using standard laboratory procedures. Data of associated risk factors were obtained with the aid of questionnaires. RESULTS Of the 444 participants, H. pylori was detected in 115 (25.9%) from culture analysis and 217 (48.9%) by direct PCR method. Ninety-eight (85.2%) of the culture-positive patients were also detected by PCR giving an overall prevalence of 52.7% (234/444). The highest number of H. pylori isolates 76.9% (180/234) was obtained from patients suffering from pangastritis. The CagA virulence gene was found in 62% (145/234), dupA in 53.4% (125/234) and vacA in 90.6% (212/234). VacA genotype s1 m1 was the most prevalent [56.4% (132)] followed by s2 m2 [11.5% (27)], s2 m1 [10.3% (24)] and [s1 m2 9.4% (22)]. There was a significant association observed in vacA s1 and peptic ulcer disease, as well as vacA s1/m2 and gastric erosion (P < 0.05). CONCLUSION The study revealed a significant association between virulence genes and the development of certain forms of gastric infections while the variations in H. pylori detection and the associated risk factors investigated in the study were not significantly related.
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Affiliation(s)
- Ayodeji Idowu
- Department of Biochemistry and Microbiology, University of Fort Hare, Alice, Eastern Cape 5700 South Africa
| | - Asisipho Mzukwa
- Department of Biochemistry and Microbiology, University of Fort Hare, Alice, Eastern Cape 5700 South Africa
| | - Ute Harrison
- Chair of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer-Institute, Faculty of Medicine, LMU Munich, Munich, Germany
| | - Pia Palamides
- Chair of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer-Institute, Faculty of Medicine, LMU Munich, Munich, Germany
| | - Rainer Haas
- Chair of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer-Institute, Faculty of Medicine, LMU Munich, Munich, Germany
| | - Melvin Mbao
- Division of Gastroenterology, Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, 2013 South Africa
| | - Razinah Mamdoo
- Division of Gastroenterology, Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, 2013 South Africa
| | - Jonathan Bolon
- Division of Gastroenterology, Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, 2013 South Africa
| | - Tolulope Jolaiya
- Department of Microbiology, University of Lagos, Akoka, Yaba Lagos Nigeria
| | - Stella Smith
- Molecular Biology Department, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria
| | - Reidwaan Ally
- Division of Gastroenterology, Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, 2013 South Africa
| | - Anna Clarke
- Department of Biochemistry and Microbiology, University of Fort Hare, Alice, Eastern Cape 5700 South Africa
| | - Henry Njom
- Department of Biochemistry and Microbiology, University of Fort Hare, Alice, Eastern Cape 5700 South Africa
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Akeel M, Shehata A, Elhafey A, Elmakki E, Aboshouk T, Ageely H, Mahfouz M. Helicobacter pylori vacA, cagA and iceA genotypes in dyspeptic patients from southwestern region, Saudi Arabia: distribution and association with clinical outcomes and histopathological changes. BMC Gastroenterol 2019; 19:16. [PMID: 30683054 PMCID: PMC6346553 DOI: 10.1186/s12876-019-0934-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 01/16/2019] [Indexed: 02/06/2023] Open
Abstract
Background The aim of this study was to identify the common H. pylori virulence genes among dyspeptic Southwestern Saudi patients and their association with clinical outcomes and histopathological findings to help practitioners and researchers in the region for better management of infections caused by such bacteria. Methods Four hundred two gastric biopsy specimens were analyzed using histopathological examination and real time-PCR. The positive 187 specimens by RT-PCR were genotyped using PCR targeting cagA, vacA and iceA genes. Results One hundred twenty-eight gastric biopsy specimens were positive in genotyping PCRs. The cagA, vacA, iceA1 and iceA2 genes were detected in rates of 49.2% (63/128), 100%(128/128), 42.2% (54/128), 32.8% (42/128), respectively. The vacA s1as1bm2 subtype was the highest 23.4% (30/128), followed by m2 and s1a1b subtypes which were equally detected [16.4% (21/128) for each]. The iceA genes were significantly associated with gastritis and gastric ulcer. Overall, vacA genotypes were significantly associated with gastritis, gastric and duodenal ulcers. The vacA subtypes: s1as1bm2, s1a1b and s2 m2 showed chronic active gastritis in percentages of 90.0, 81, and 84.2%, respectively. All vacA mixed genotypes showed chronic active gastritis. Conclusions H. pylori virulence genes are highly prevalent and diverse among patients with dyspepsia in Southwestern region of Saudi Arabia. The iceA genes and the different vacA subtypes are significantly associated with the clinical outcomes and histopathological changes especially chronic active gastritis.
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Affiliation(s)
- Mohammed Akeel
- Department of Anatomy, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia.
| | - Atef Shehata
- Department of Microbiology and Immunology, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia.,Department of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Ahmed Elhafey
- Department of Pathology, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia.,Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Erwa Elmakki
- Department of Internal Medicine, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Thanaa Aboshouk
- Department of Biochemistry, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Hussein Ageely
- Department of Internal Medicine, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia
| | - Mohammed Mahfouz
- Department of Family and Community Medicine, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia
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Sheikh AF, Yadyad MJ, Goodarzi H, Hashemi SJ, Aslani S, Assarzadegan MA, Ranjbar R. CagA and vacA allelic combination of Helicobacter pylori in gastroduodenal disorders. Microb Pathog 2018; 122:144-150. [PMID: 29908307 DOI: 10.1016/j.micpath.2018.06.023] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/12/2018] [Accepted: 06/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Allelic variation of the virulence genes, vacA and cagA, as the most important virulence associated genes play an important role in the pathogenesis of severe gastrointestinal disease. OBJECTIVE The aim of the present study was to identify the diversity of the virulence genes in patients with Gastric Cancer (GC), who were referred to the gastro-endoscopy unit of Imam Khomeini Hospital, Ahvaz Jundishapur University of medical science, Ahvaz, Iran. METHODS Gastric biopsy specimens from 301 patients suspected to gastrointestinal disorders, were analyzed for H. pylori using molecular and phenotypical methods (culture, and biochemical test (catalase, oxidase and urease tests)). RESULTS Among 201 PCR positive for H. pylori, using histopathological methods, 22 (10.9%) patients had GC. Presence of vacA gene in our H. pylori strains was 100% (201/201), while the most virulent vacA s1 allele was detected in 82.6% isolates, and the mid region vacA m1 was found in 39.8% isolates. The vacA s1/m1 genotype was the most virulent allelic combination in GC and Peptic Ulcer Disease (PUD) in 68.2% and 50%, respectively. The cagA gene was detected in 66.7% isolates. Among the cagA positive isolates, EPIYA-ABC motif was the most common motif in the GC (66.7%), PUD (55.6%) and Erosive Gastroduodenitis (EG) samples (55.2%), while EPIYA-ABCC was the most common motif (58.7%) in the Non-Ulcer Dyspepsia (NUD) samples. The vacA s1m1/cagA+ combination was detected in GC (73.3%) and PUD (51.9%), while vacA s1m2/cagA+ presented in the NUD and EG samples in 77.8% and 62.1%, respectively. CONCLUSION In this work, Western type (EPIYA-ABC and ABCC motifs) cagA, vacA s1m1 combinations have been demonstrated as the dominant genotype in the tested Ahvazian H. Pylori strains. Also the participation of cagA gene and vacA s1m1 genotype in development and severity of gastric disorder was well evident. Therefore, infection with H. pylori strain containing the cagA gene or the vacA s1m1 genotypes could be associated with increased risk of GC. This is the first study in our area that reports the high incidence and diversity of allelic combination of cagA and vacA genes in gastroduodenitis patients.
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Affiliation(s)
- Ahmad Farajzadeh Sheikh
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammad Jaafar Yadyad
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hamed Goodarzi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Molecular Biology Research Center, Baqiyatallah University of Medical Science, Tehran, Iran.
| | - Seyed Jalal Hashemi
- Research Institute for Infectious Diseases of the Digestive System, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Division of Gastroenterology and Hepatology, Ahvaz Jundishapur University of Medical Sciences, Ahwaz, Iran.
| | - Sajad Aslani
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Reza Ranjbar
- Molecular Biology Research Center, Baqiyatallah University of Medical Science, Tehran, Iran.
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Abu-Taleb AMF, Abdelattef RS, Abdel-Hady AA, Omran FH, El-korashi LA, Abdel-aziz El-hady H, El-Gebaly AM. Prevalence of Helicobacter pylori cagA and iceA Genes and Their Association with Gastrointestinal Diseases. Int J Microbiol 2018; 2018:4809093. [PMID: 29849647 PMCID: PMC5907521 DOI: 10.1155/2018/4809093] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 02/15/2018] [Accepted: 02/20/2018] [Indexed: 12/20/2022] Open
Abstract
H. pylori infection causes peptic ulcer, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma. It has several virulence factors such as cytotoxin-associated gene A(cagA) and the induced by contact with epithelium antigen (iceA). We aimed to explore the relationship between cagA and iceA of H. pylori and gastrointestinal diseases. One hundred and eighteen patients who attended Gastrointestinal Endoscopy Unit at Zagazig University Hospitals, Egypt, were included in this study. Two gastric biopsies were collected and evaluated by rapid urease test (RUT) and PCR. cagA and iceA genes were amplified by PCR. We found that 54 patients (45.76%) were positive by both RUT and PCR. cagA and iceA genes were present in 57.4% and 46.29% of the studied patients, respectively. cagA was the most prevalent gene in gastritis (33.3%) and peptic ulcer (68.7%). iceA1/iceA2 positive genes were the most prevalent in gastric cancer (75%). iceA1 gene was present in 38.7% of cagA positive cases, but iceA2 gene was present in 45.2% of cagA positive cases. iceA1/iceA2 positive genes were present in 29% of cagA positive cases. In conclusion, cagA and iceA genes could be used as markers for severe gastrointestinal diseases. iceA gene was strongly related to cagA gene.
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Affiliation(s)
- Ashwak M. F. Abu-Taleb
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Randa S. Abdelattef
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amina A. Abdel-Hady
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Farida H. Omran
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Lobna A. El-korashi
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | | | - Ahmed M. El-Gebaly
- Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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25
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Brennan DE, Dowd C, O’Morain C, McNamara D, Smith SM. Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection? World J Gastroenterol 2018; 24:971-981. [PMID: 29531461 PMCID: PMC5840472 DOI: 10.3748/wjg.v24.i9.971] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/05/2018] [Accepted: 02/08/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori (H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. cagA and vacA genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5% (n = 53/105), 78.3% (n = 47/60) and 60.6% (n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2% (n = 16/105) and 28.3% (n = 17/60) and 20% (n = 33/165), respectively. Resistance to both antibiotics was 12.4% (n = 13/105) in treatment-naïve patients, 25% (n = 15/60) in those previously treated and 17% (n = 28/165) overall. A cagA-positive genotype was detected in 22.4% (n = 37/165) of patient samples. The dominant vacA genotype was S1/M2 at 44.8% (n = 74/165), followed by S2/M2 at 26.7% (n = 44/165), S1/M1 at 23.6% (n = 39/165) and S2/M1 at 4.8% (n = 8/165). Primary clarithromycin resistance was significantly lower in cagA-positive strains than in cagA-negative strains [32% (n = 8/25) vs 56.3% (n = 45/80) P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, [41% (n = 32/78) vs 77.8% (n = 21/27) P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status. CONCLUSION Genotypic H. pylori clarithromycin resistance is high and cagA-negative strains are dominant in our population. Less virulent (cagA-negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.
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Affiliation(s)
- Denise E Brennan
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
| | - Colin Dowd
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
| | - Colm O’Morain
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
| | - Deirdre McNamara
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
| | - Sinéad M Smith
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D2, Ireland
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26
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Saeidi Y, Pournajaf A, Gholami M, Hasannejad-Bibalan M, Yaghoubi S, Khodabandeh M, Emadi B, Ferdosi-Shahandashti E, Rajabnia R. Determination of Helicobacter pylori virulence-associated genes in duodenal ulcer and gastric biopsies. Med J Islam Repub Iran 2017; 31:95. [PMID: 29951396 PMCID: PMC6014795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Indexed: 11/25/2022] Open
Abstract
Background:Helicobacter pylori (H. pylori or Hp) has been strongly associated with the peptic ulcer diseases, chronic gastritis, ulcers, and gastric cancer. Genes associated with pathogenicity have been designated for H. pylori, and some of them appear to be related to more severe clinical consequences of the infection. The present study was conducted to determine cagA, vacA, cagE, iceA1, oipA, and iceA2 genes in H. pylori strains isolated from gastroduodenal patients, who referred to Shariati hospital in Tehran, Iran. Methods: Gastric biopsy specimens were collected during endoscopy from patients, who referred to the Shariati hospital in Tehran, Iran during January and November 2015. After isolation of H. pylori from the biopsy culture, genomic DNA was extracted and subsequently used to identify H. pylori and virulence genes using specific primers. Results: The isolation rate of H. pylori strains was 65.7% (169/257). The frequency of cagA, vacA, cagE, iceA1, oipA, and iceA2 was 143 (% 84.6), 169 (100%), 131 (77.5%), 97 (57.3%), 89 (52.6%), and 72 (42.6%), respectively. Conclusion: In this study, a significant difference was observed between investigated genes and strains isolated from PUD and GC patients (p<0.05).
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Affiliation(s)
- Yasaman Saeidi
- 1 Department of Microbiology, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Abazar Pournajaf
- 2 Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Mehrdad Gholami
- 2 Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Meysam Hasannejad-Bibalan
- 2 Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Sajad Yaghoubi
- 3 Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mahmoud Khodabandeh
- 4 Department of Pediatric Infectious Disease, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Behzad Emadi
- 5 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, International campus, Tehran, Iran.
| | - Elaheh Ferdosi-Shahandashti
- 6 Department of Medical Biotechnology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
| | - Ramazan Rajabnia
- 7 Infectious Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran.
,Corresponding author: Dr Ramazan Rajabnia,
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27
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Klymiuk I, Bilgilier C, Stadlmann A, Thannesberger J, Kastner MT, Högenauer C, Püspök A, Biowski-Frotz S, Schrutka-Kölbl C, Thallinger GG, Steininger C. The Human Gastric Microbiome Is Predicated upon Infection with Helicobacter pylori. Front Microbiol 2017; 8:2508. [PMID: 29312210 PMCID: PMC5735373 DOI: 10.3389/fmicb.2017.02508] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 12/01/2017] [Indexed: 12/18/2022] Open
Abstract
The human gastric lumen is one of the most hostile environments of the human body suspected to be sterile until the discovery of Helicobacter pylori (H.p.). State of the art next generation sequencing technologies multiply the knowledge on H.p. functional genomics as well as on the colonization of supposed sterile human environments like the gastric habitat. Here we studied in a prospective, multicenter, clinical trial the 16S rRNA gene amplicon based bacterial microbiome in a total of 30 homogenized and frozen gastric biopsy samples from eight geographic locations. The evaluation of the samples for H.p. infection status was done by histopathology and a specific PCR assay. CagA status was determined by a CagA-specific PCR assay. Patients were grouped accordingly as H.p.-negative, H.p.-positive but CagA-negative and H.p.-positive and CagA-positive (n = 10, respectively). Here we show that H.p. infection of the gastric habitat dominates the gastric microbiota in most patients and is associated with a significant decrease of the microbial alpha diversity from H.p. negative to H.p. positive with CagA as a considerable factor. The genera Actinomyces, Granulicatella, Veillonella, Fusobacterium, Neisseria, Helicobacter, Streptococcus, and Prevotella are significantly different between the H.p.-positive and H.p.-negative sample groups. Differences in microbiota found between CagA-positive and CagA-negative patients were not statistically significant and need to be re-evaluated in larger sample cohorts. In conclusion, H.p. infection dominates the gastric microbiome in a multicentre cohort of patients with varying diagnoses.
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Affiliation(s)
- Ingeborg Klymiuk
- Center for Medical Research, Medical University of Graz, Graz, Austria
| | - Ceren Bilgilier
- Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Alexander Stadlmann
- Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Jakob Thannesberger
- Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Marie-Theres Kastner
- Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Christoph Högenauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Püspök
- Department of Internal Medicine II, St. John's Hospital Eisenstadt, Eisenstadt, Austria
| | - Susanne Biowski-Frotz
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria
| | - Christiane Schrutka-Kölbl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria
| | - Gerhard G. Thallinger
- Institute of Computational Biotechnology, Graz University of Technology, Graz, Austria
- BioTechMed OMICS Center Graz, Graz, Austria
| | - Christoph Steininger
- Division of Infectious Diseases, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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28
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Detection of Helicobacter pylori vacA , cagA and iceA1 virulence genes associated with gastric diseases in Egyptian patients. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2017. [DOI: 10.1016/j.ejmhg.2017.04.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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29
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Lucero Y, Oyarzún A, O'Ryan M, Quera R, Espinosa N, Valenzuela R, Simian D, Alcalde E, Arce C, Farfán MJ, Vergara AF, Gajardo I, Mendez J, Carrasco J, Errázuriz G, Gonzalez M, Ossa JC, Maiza E, Perez-Bravo F, Castro M, Araya M. Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients. Front Cell Infect Microbiol 2017; 7:376. [PMID: 28879170 PMCID: PMC5572207 DOI: 10.3389/fcimb.2017.00376] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/08/2017] [Indexed: 12/14/2022] Open
Abstract
HIGHLIGHTS
What is already known about this subject? Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive. H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways. The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated. What are the new findings? cagA+ H. pylori strains are associated to milder histological damage in infected CD patients. In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals. How might it impact on clinical practice in the foreseeable future? The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.
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Affiliation(s)
- Yalda Lucero
- Hospital Dr. Luis Calvo MackennaSantiago, Chile.,Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, University of ChileSantiago, Chile.,Microbiology and Micology Program, Faculty of Medicine, University of ChileSantiago, Chile
| | - Amaya Oyarzún
- Laboratory of Immunegenetics, Institute of Nutrition and Food Technology, University of ChileSantiago, Chile
| | - Miguel O'Ryan
- Microbiology and Micology Program, Faculty of Medicine, University of ChileSantiago, Chile.,Millenium Institute of Immunology and Immunotherapy, Faculty of Medicine, University of ChileSantiago, Chile
| | - Rodrigo Quera
- Department of Gastroenterology, Clínica Las CondesSantiago, Chile
| | | | - Romina Valenzuela
- Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, University of ChileSantiago, Chile
| | - Daniela Simian
- Department of Gastroenterology, Clínica Las CondesSantiago, Chile
| | | | | | - Mauricio J Farfán
- Hospital Dr. Luis Calvo MackennaSantiago, Chile.,Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, University of ChileSantiago, Chile
| | | | - Iván Gajardo
- Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, University of ChileSantiago, Chile
| | | | | | - Germán Errázuriz
- Department of Gastroenterology, Clínica Las CondesSantiago, Chile
| | | | - Juan C Ossa
- Hospital Dr. Luis Calvo MackennaSantiago, Chile.,Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, University of ChileSantiago, Chile
| | | | | | - Magdalena Castro
- Millenium Institute of Immunology and Immunotherapy, Faculty of Medicine, University of ChileSantiago, Chile
| | - Magdalena Araya
- Microbiology and Micology Program, Faculty of Medicine, University of ChileSantiago, Chile
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Medina ML, Medina MG, Merino LA. Correlation between virulence markers of Helicobacter pylori in the oral cavity and gastric biopsies. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:217-221. [PMID: 28724047 DOI: 10.1590/s0004-2803.201700000-24] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Accepted: 03/27/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND: The clinical outcome of Helicobacter pylori infection has been associated with virulence factors. The presence of these factors is useful as molecular markers in the identification of the high risk for developing severe gastric pathologies. OBJECTIVE: To correlate the presence of virulence markers cagA and bab2A of H. pylori in oral and gastric biopsy samples. METHODS: An observational, prospective, descriptive, and cross-sectional study was carried out between September 2011 and September 2012. Patients suffering dyspepsia with indication for upper gastrointestinal video endoscopy who attended the Gastroenterology Service of the Hospital Dr. Julio C. Perrando were included. Epidemiological investigation was completed. To detect the bacteria and their virulence genes, samples of saliva, dental plaque and gastric biopsy were taken and processed by PCR. RESULTS: Sixty-one patients were selected for this study (30 women and 31 men). H. pylori was detected in 31 gastric biopsies and 31 oral samples. Significant difference between oral and gastric samples was found in cagA genotype. Agreement between oral and gastric genotypes was found in 38.7% of samples from the same patient. CONCLUSION: This study is the first in provide information about the genotypes of the Argentinean Northeast H. pylori strains. Despite the high prevalence of H. pylori infection, the most of patients had less virulent genotypes in oral cavity and gastric tissue. The cagA / babA2 combination was not frequent in the samples studied. There was not a statistical correlation between the virulence genes and gastroduodenal or oral diseases. Although in some patients the same genotype was found both in oral and gastric samples, it cannot be ensure that they corresponding to the same strain because a DNA sequencing was not performed.
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Affiliation(s)
- Myriam Lucrecia Medina
- Unidad de Investigación, Hospital Pediátrico Dr. Avelino Castelán, Resistencia, Argentina
| | - Marcelo Gabriel Medina
- Area de Medicina Tropical, Instituto de Medicina Regional, Universidad Nacional del Nordeste, Resistencia, Argentina
| | - Luis Antonio Merino
- Area de Bacteriología, Instituto de Medicina Regional, Universidad Nacional del Nordeste, Resistencia, Argentina
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Talebi Bezmin Abadi A, Perez-Perez G. Role of dupA in virulence of Helicobacter pylori. World J Gastroenterol 2016; 22:10118-10123. [PMID: 28028359 PMCID: PMC5155170 DOI: 10.3748/wjg.v22.i46.10118] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 09/27/2016] [Accepted: 11/14/2016] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.
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Abstract
This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.
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Affiliation(s)
- Mārcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia.,Riga East University Hospital, Riga, Latvia.,Digestive Diseases Centre GASTRO, Riga, Latvia
| | | | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Talaei R, Souod N, Momtaz H, Dabiri H. Milk of livestock as a possible transmission route of Helicobacter pylori infection. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2015. [PMID: 26171135 DOI: 10.22037/ghfbb.v8isupplement.764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM The current investigation aimed to evaluate ruminant raw milk as a reservoir source of Helicobacter pylori and analyze the diversity of cagA and vacA genotypes as H. pylori virulence factors to find any relationship between these genotypes in human and animal H. pylori strains. BACKGROUND The way of transmission of Helicobacter pylori as one of the most controversial bacteria in the world, which colonizes the human gastric tissue and is responsible for several gastric diseases is still unknown. The possibility of zoonotic transmission of H. pylori is feasible, but is not proven in ruminant reservoirs. METHODS Overall 210 cows, sheep, goats, camels and buffalos' raw milk samples and 100 human gastric biopsies were collected in this survey. We applied PCR assays to identify H. pylori, vacA and cagA genes. Statistical tests were applied for data analysis. RESULTS Totally 12(16%) cow, 8(13.79%) sheep, 2 (4.76%) goat, 2(13.33%), buffalo 4(20%) and 82 (82%) of human specimens were confirmed to be H. pylori positive. Among which s1a/m2 genotype was more frequent in isolated H. pylori strains and statistically significant between strains. Based on statistical analyses the s1b allele of sheep had a significant association with human strains. CONCLUSION The current survey was prompted by our previous report. According to both results we can conclude that sheep may act as a reservoir for H. pylori and transmit this bacterium to human via its milk. Extended assessments in other geographical regions and other animals are recommended.
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Affiliation(s)
- Ramin Talaei
- Shahid Modaress Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Negar Souod
- Young Researchers and Elite Club, Islamic Azad University, Central Tehran Branch, Tehran, Iran
| | - Hassan Momtaz
- Department of Microbiology, Faculty of Veterinary Medicine, Islamic Azad University, ShahreKord Branch, ShahreKord, Iran
| | - Hossein Dabiri
- Department of Clinical Microbiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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