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Buyuk F, Karakaya E, Akar M, Kayman T, Tarhane S, Ozcan HE, Celebi O, Saticioglu IB, Anuk T, Abay S, Otlu S, Aydin F. A comprehensive study of Helicobacter pylori infection: molecular analysis, antibacterial susceptibility, and histopathological examination. Antonie Van Leeuwenhoek 2023; 116:1261-1273. [PMID: 37603113 DOI: 10.1007/s10482-023-01868-3] [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: 02/14/2023] [Accepted: 08/07/2023] [Indexed: 08/22/2023]
Abstract
Helicobacter pylori is a pathogen associated with gastroduodenal diseases. This study aimed; (i) to investigate H. pylori presence by invasive tests in adult dyspeptic patients, (ii) to determine antibiotic susceptibility and genotypic characteristics of the H. pylori isolates, and (iii) to investigate the relationship between the H. pylori genotypes and the histopathological findings. In this cross-sectional study, gastric biopsy samples from 208 adult dyspeptic patients were used for culture, tissue Polymerase Chain Reaction (PCR), and histopathological analysis. Antibiotic susceptibility of the H. pylori isolates was analyzed by gradient method. Analysis of the virulence genes was performed by monoplex PCR. Genetic profiles (from A to H) were created based on the virulence genes presence. Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR) was used for the genotyping of the H. pylori isolates. The mean age of the patients was 46 (± 15) years and 128 (61.5%) of them were female. H. pylori positivity was detected by culture, tissue PCR and histopathological examination in 59 (28.4%), 114 (54.8%) and 81 (38.9%) patients, respectively. The overall prevalence of H. pylori was found to be 63% (131/208). All H. pylori isolates were susceptible to tetracycline and amoxicillin. The resistance rates for metronidazole, clarithromycin, levofloxacin, and rifampicin were 67.2%, 27.9%, 34.4% and 13.11%, respectively. Multi drug resistance (MDR) was detected at the rate of 45.9% (28/61). While the most common virulence gene was cagA (93.44%), the least common was vacAm1 (23%). The predominant genetic profile was profile A (47.5%). ERIC-PCR results revealed a total of 26 different patterns. A high prevalence of H. pylori was detected in adult dyspeptic patients as in developing countries. It was observed significant genotypic heterogeneity and virulence gene diversity within the isolates. A considerable resistance rate detected against antibiotics such as clarithromycin, metronidazole, and levofloxacin, which are frequently used in the eradication of H. pylori, should be taken into consideration when creating regional empirical treatment regimens.
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Affiliation(s)
- Fatih Buyuk
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye.
| | - Emre Karakaya
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
| | - Mustafa Akar
- Department of Gastroenterology, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Türkiye
| | - Tuba Kayman
- Department of Medical Microbiology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Türkiye
| | - Serdal Tarhane
- Veterinary Department, Eldivan Vocational School of Health Services, Çankırı Karatekin University, Çankırı, Türkiye
| | - Hacer Ece Ozcan
- Department of Medical Pathology, Mersin City Hospital, Mersin, Türkiye
| | - Ozgur Celebi
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye
| | - Izzet Burcin Saticioglu
- Department of Aquatic Animal Diseases, Faculty of Veterinary Medicine, Uludağ University, Bursa, Türkiye
| | - Turgut Anuk
- Department of General Surgery, Erzurum Faculty of Medicine, University of Health Sciences, Erzurum, Türkiye
| | - Secil Abay
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
| | - Salih Otlu
- Department of Microbiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Türkiye
| | - Fuat Aydin
- Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Türkiye
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Svarval AV, Starkova DA, Ferman RS. Virulence determinants and genotypes of <i>Helicobacter pylori</i> clinical isolates. JOURNAL OF MICROBIOLOGY, EPIDEMIOLOGY AND IMMUNOBIOLOGY 2023. [DOI: 10.36233/0372-9311-298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Background. H. pylori is the principal causative agent of gastroduodenal disorders in humans. The development and severity of lesions in infected individuals depend on the virulence of H. pylori strains.
Aims: Detection of virulence determinants and comparative analysis of H. pylori genotypes in patients with chronic gastritis (CG) and duodenal ulcer (DU).
Materials and methods. The 53 H. pylori strains were isolated in St. Petersburg from patients with CG (n = 34) and DU (n = 19). The genetic determinants of virulence cagA, iceA, vacA and H. pylori genotypes in patients with CG and UC were determined using the standard PCR method.
Results. The cagA gene was found in 64.1% of H. pylori strains. The proportions of cagA+ isolates from patients with CG and DU was 55.8% (15/34) and 78.9% (15/19), respectively (p 0.05). The iceA1 allele of H. pylori was detected in 47.4% of patients with DU, the iceA2 in 47.1% of patients with CG (p 0.05). The vacAs1 allele was significantly dominant in patients with DU 94.7% versus 70.6% in CG (p 0.05). No significant difference in vacA m1 and m2 alleles was found in H. pylori from different groups of patients (p 0.05). All cagA+ strains were carriers of the vacA s1 allele. The vast majority of strains (10 out of 11) of the cagA/vacAs2 genotype were isolated from patients with CG.
Conclusion. The significant association between vacAs1, vacAs2 allelic variants, as well as vacA s1/m2, vacA s2/m2 genotypes of the pathogen and severity of clinical manifestations of H. pylori infection has been established in our study. The vacAs1 and vacA s1/m2 genotypes of the pathogen are associated with duodenal ulcer.
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Li Y, Jiang L, Li Z, Liu Y, Xiao B, Ding Y, Wen H. Differences in gastric microbiota and mucosal function between patients with chronic superficial gastritis and intestinal metaplasia. Front Microbiol 2022; 13:950325. [PMID: 36466659 PMCID: PMC9712754 DOI: 10.3389/fmicb.2022.950325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 10/24/2022] [Indexed: 11/26/2023] Open
Abstract
Chronic superficial gastritis (CSG) and intestinal metaplasia (IM) can further develop into gastric cancer, which seriously endangers the health of people all over the world. In this study, the differences in gastric microbiota between CSG patients and IM patients were detected by 16S rRNA gene sequencing. As the expression levels of mucin and CDX2 are closely related to IM, the expression differences of mucin (MUC2 and MUC5AC) and CDX2 in the gastric mucosa of CSG patients and IM patients were detected by Western blot and qRT-PCR. The results showed that both Faith_pd and Observed_species indexes of microbiota in the gastric juice of CSG patients were significantly higher than those of IM patients. At the genus level, Thermus and Anoxybacillus were dominant in the gastric juice of IM patients, and Helicobacter was dominant in the gastric juice of CSG patients. Non-metric multidimensional scaling (NMDS) demonstrated that the dispersion of samples in the CSG group is greater than that in the IM group, and some samples in the CSG group are clustered with samples in the IM group. The KEGG metabolic pathway difference analysis of gastric juice microbiota in CSG and IM patients revealed that the gastric juice microbiota in the CSG and IM patients were significantly enriched in the amino acid metabolism, carbohydrate metabolism, and metabolism of cofactors and vitamins, and the functional differences between the two groups were mainly concentrated in the bacterial secretion system (VirB1, VirB2, VirB3, VirD2, and VirD4). In conclusion, there are significant differences in gastric microbiota and mucosal function between the CSG and IM patients. Moreover, the results of this study may provide a new means for the detection of CSG and IM and a new direction for the prevention and treatment of CSG and IM.
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Affiliation(s)
- Yingxia Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Libin Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhichao Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, China
| | - Yali Liu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bo Xiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Ding
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hongtao Wen
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Svarval AV, Starkova DA, Ferman RS. Detection of the babA2 adhesin protein gene in Helicobacter pylori clinical isolates. Klin Lab Diagn 2022; 67:538-543. [PMID: 36099464 DOI: 10.51620/0869-2084-2022-67-9-538-543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The study compared the effectiveness of two different primer sets for detecting and evaluating the prevalence of the babA2 gene in 52 H. pylori clinical isolates from patients with chronic gastritis (n=32), duodenal ulcer (n=16) and stomach cancer (n=4) in St. Petersburg, Russia. The PCR was used for detection of the babA2 gene with 271 bp and 832 bp primer sets followed by sequencing of the PCR-amplicons. The largest proportion of babA2-positive strains - 90.4% (47/52) was detected using a 271 bp PCR primer set. Detection of the 832 bp PCR positive samples was observed only in 51.9% of cases (27/52). The largest proportion of babA2-positive strains - 90.4% (47/52) was detected using 271 bp PCR primer set; detection of 832 bp PCR product was observed only in 51.9% cases (27/52), however, there were no significant differences in the babA2 gene detection rates (p>0.05). Bioinformatic analysis revealed a homology of Sanger sequenced PCR products 271 bp and 832 bp of babA2 gene with regions of the babA2, babA1, and chimeric babA/B genes of H. pylori strains annotated in the NCBI database. Regardless of the primer set used, the presence of babA2 was not significantly associated with duodenal ulcer nor gastric cancer (p>0.05). The combination of the three babA2, cagA, and vacAs1 genes did not reveal any association between the presence of babA2 gene and cagA/vacAs1 genes in H. pylori strains (p>0.05). Thus, none of the two primer sets (271 bp and 832 bp) appears sufficiently informative for detecting the babA2 gene to assess virulence of H. pylori Russian strains.
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Hosseini RS, Rahimian G, Shafigh MH, Validi M, Khaledi M, Gholipour A. Correlation between clarithromycin resistance, virulence factors and clinical characteristics of the disease in Helicobacter pylori infected patients in Shahrekord, Southwest Iran. AMB Express 2021; 11:147. [PMID: 34731345 PMCID: PMC8566624 DOI: 10.1186/s13568-021-01310-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022] Open
Abstract
The purpose of this study was to determine the mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from biopsy samples that were collected from the endoscopic ward of Shahrekord Hajar teaching Hospital and also to study the frequency of virulence factor and their correlation and pathological findings with clarithromycin resistance during the years 2019-2020. In this cross-sectional descriptive study, 152 patients with Helicobacter pylori infection were considered, and then, two common A2142G and A2143G mutations in the 23SrRNA gene associated with resistance were analyzed by Real-time PCR (Taq man). The presence of vacA, iceA1, iceA2, cagA, babA2, and oipA virulence genes was investigated by PCR and electrophoresis in 8% polyacrylamide gel. Then, data were analyzed using the relevant statistical tests. In this study, the frequency of Helicobacter pylori was 76% and the frequency of mutant isolates was 57.2%. The frequencies of A2142G and A2143G point mutations were 42.1% and 28.3%. There was a significant correlation among oipA, vacA, and iceA1 virulence factors, type of disease, chronic inflammatory score, and glandular atrophy with the antibiotic resistance to clarithromycin. There was no significant correlation between the age and sex of the patients with antibiotic resistance. According to the results of this study, it seems that the use of clarithromycin to combat this bacterium should be limited.
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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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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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Prevalence of the Helicobacter pylori babA2 Gene in Children Mainly Depends on the PCR Primer Set Used. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2020; 2020:4080248. [PMID: 32855749 PMCID: PMC7443014 DOI: 10.1155/2020/4080248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023]
Abstract
Various polymerase chain reaction- (PCR-) based methods with varying positivity rates were designed to detect the Helicobacter pylori babA2 gene. To compare different primer sets, babA2 prevalence was determined in 279 H. pylori-positive pediatric samples using the 832 bp, 139 bp, and 271 bp PCR primer sets, resulting in 34.0%, 51.3%, and 79.6% prevalence of the babA2 gene, respectively. The babA2 status determined using the 832 bp and 139 bp PCR primer sets significantly correlated with bacterial density and activity of inflammation, whereas no such correlations were found using the 271 bp PCR primer set. The 139 and 832 bp PCR primer sets concordantly detected the babA2 gene in 93 cases; however, in comparison to the 832 bp PCR primer set, the 139 bp PCR primer set detected additional 50 babA2 cases, whereas only two 832 bp positive cases were missed. The 271 bp PCR primer set missed 32 babA2 cases that were 832 bp and/or 139 bp PCR positive, but tested solely positive in 109 cases. Interestingly, cloning of a subset of 271 bp PCR positive samples revealed amplification of the babA/B gene chimera. Hence, in our opinion, the 271 bp PCR protocol is not a reliable diagnostic tool for detecting the babA2 gene in children. Our results reaffirm previous observations that the use of certain babA2 PCR primer sets can significantly impact estimation of the prevalence and clinical relevance of the H. pylori babA2 gene in children, suggesting babA2 detection methods should be carefully selected.
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Precancerous Gastric Lesions with Helicobacter pylori vacA +/ babA2 +/ oipA + Genotype Increase the Risk of Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7243029. [PMID: 32149129 PMCID: PMC7049835 DOI: 10.1155/2020/7243029] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/25/2019] [Accepted: 12/24/2019] [Indexed: 12/12/2022]
Abstract
Objective The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of Results H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of vacA, babA2, and oipA genes and their association with clinical outcomes. vacA, babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.033, OR = 2.64; 95% CI = 1.44–4.82, H. pylori vacA+/babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR = 2.64; 95% CI = 1.44–4.82, Conclusion In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of H. pylori vacA+/babA2, and oipA genes and their association with clinical outcomes.
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Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019; 25:4870-4884. [PMID: 31543679 PMCID: PMC6737321 DOI: 10.3748/wjg.v25.i33.4870] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.
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Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Erika Jarc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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Korona-Glowniak I, Cichoz-Lach H, Siwiec R, Andrzejczuk S, Glowniak A, Matras P, Malm A. Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland. J Clin Med 2019; 8:1071. [PMID: 31330898 PMCID: PMC6678771 DOI: 10.3390/jcm8071071] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/15/2019] [Accepted: 07/18/2019] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(-)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder.
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Affiliation(s)
- Izabela Korona-Glowniak
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland.
| | - Halina Cichoz-Lach
- Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Radoslaw Siwiec
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
| | - Sylwia Andrzejczuk
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
| | - Andrzej Glowniak
- Department of Cardiology, Medical University of Lublin, 20-090 Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Przemyslaw Matras
- Chair and Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Anna Malm
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
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Rapid Characterization of Virulence Determinants in Helicobacter pylori Isolated from Non-Atrophic Gastritis Patients by Next-Generation Sequencing. J Clin Med 2019; 8:jcm8071030. [PMID: 31336977 PMCID: PMC6678415 DOI: 10.3390/jcm8071030] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 07/09/2019] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori is a major human pathogen that causes a wide range of gastrointestinal pathology. Progression of H. pylori induced gastritis to more severe disease has been found to highly correlate with the array of virulence factors expressed by the pathogen. The objective of this study was twofold: first, to characterize the genetic diversity of H. pylori strains isolated from 41 non-atrophic gastritis patients in Switzerland, an issue that has not been investigated to date. And second, to assess the prevalence and sequence variation of H. pylori virulence factors (cagA, vacA, iceA and dupA) and genes encoding outer membrane proteins (OMPs; babA, babB, sabA, sabB, hopZ, hopQ and oipA) by whole genome sequencing (WGS) using an Illumina MiSeq platform. WGS identified high genetic diversity in the analyzed H. pylori strains. Most H. pylori isolates were assigned to hpEurope (95.0%, 39/41), and the remaining ones (5.0%, 2/41) to hpEastAsia, subpopulation hspEAsia. Analysis of virulence factors revealed that 43.9% of the strains were cagA-positive, and the vacA s1 allele was detected in 56.0% of the isolates. The presence of cagA was found to be significantly associated (P < 0.001) with the presence of vacA s1, babA2 and hopQ allele 1 as well as expression of oipA. Moreover, we found an association between the grade of gastritis and H. pylori abundance in the gastric mucosa, respectively and the presence of cagA, vacA s1 and hopQ allele 1. Among our 41 gastritis patients, we identified seven patients infected with H. pylori strains that carried a specific combination of virulence factors (i.e., cagA, vacA s1 allele and babA2 allele), recently implicated in the development of more severe gastrointestinal pathology, like peptic ulcer disease and even gastric cancer. To this end, WGS can be employed for rapid and detailed characterization of virulence determinants in H. pylori, providing valuable insights into the pathogenic capacity of the bacterium. This could ultimately lead to a higher level of personalized treatment and management of patients suffering from H. pylori associated infections.
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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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Sohrabi M, Khashei R, Alizadeh M, Asl MKH, Nejati MA, Dara M, Bazargani A. Low Rate of babA2 Genotype among Iranian Helicobacter pylori Clinical Isolates. J Clin Diagn Res 2017; 11:DC32-DC36. [PMID: 28892894 DOI: 10.7860/jcdr/2017/24810.10277] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 05/04/2017] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The Blood Group Antigen-Binding Adhesion (babA), Outer Inflammatory Protein (oipA) and Sialic Acid-Binding Adhesin (sabA) as outer membrane proteins involved in Helicobacter pylori adherence to gastric mucosa have been suggested to have a role in the pathogenesis. AIM To investigate the frequency of H. pylori isolates babA2, oipA and sabA genes in Iranian dyspeptic patients. MATERIALS AND METHODS DNAs were extracted from H. pylori -positive cultures taken from 100 different dyspeptic patients. Genotyping was performed by Polymerase Chain Reaction (PCR), using the specific primers for babA2, oipA and sabA genes. Chi square test was used to investigate association between variables, p<0.05 was considered statistically significant. RESULTS All (100%) isolates possessed oipA and sabA genotypes, whereas babA2 was detected in 22% of isolates. There was no significant relationship between presence of genes with clinical outcome. The combined genotype oipA +/sabA +/ babA2- was correlated with gastritis. The rate of babA2 genotype in our isolates was lower than other Iranian reports. CONCLUSION Frequency of babA2 genotype among H. pylori isolates from Southwest of Iran is considerably less than other regions of Iran. Due to heterogeneity of H. pylori strains in different geographic regions, further work will be needed to understand the role of these virulence genes in H. pylori pathogenesis and their possible association with disease outcome.
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Affiliation(s)
- Maryam Sohrabi
- Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Khashei
- Assistant Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahvash Alizadeh
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Kazem Hosseini Asl
- Associate Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Ali Nejati
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahintaj Dara
- Ph.D Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abdollah Bazargani
- Associate Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Ansari S, Yamaoka Y. Helicobacter pylori BabA in adaptation for gastric colonization. World J Gastroenterol 2017; 23:4158-4169. [PMID: 28694656 PMCID: PMC5483490 DOI: 10.3748/wjg.v23.i23.4158] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/12/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) as a causative agent of gastric complications, is well adapted for the colonization of gastric mucosa. Although the infectious process depends on several factors, the adhesion to the gastric mucosa is the first and important step. Among several outer membrane proteins, BabA is one of the significant protein involving in many inflammatory processes in addition to its role in the attachment for the persistent colonization. We performed a PubMed search using the key words: “babA”, “pylori”, “gastric complications”, “homologous recombination”, “slipped strand mispairing”; a total of 249 articles were displayed. Of these we mainly focused on articles with the full text in English and published between 2005 and 2016. H. pylori BabA is involved in binding with receptors; however, its synthesis is regulated by phase variation. In this review we confirm that H. pylori babA can be modulated at the molecular and functional levels to adapt to the stress within the gastro-intestinal tract.
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Dabiri H, Jafari F, Baghaei K, Shokrzadeh L, Abdi S, Pourhoseingholi MA, Mohammadzadeh A. Prevalence of Helicobacter pylori vacA, cagA, cagE, oipA, iceA, babA2 and babB genotypes in Iranian dyspeptic patients. Microb Pathog 2017; 105:226-230. [PMID: 28215588 DOI: 10.1016/j.micpath.2017.02.018] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Revised: 02/08/2017] [Accepted: 02/13/2017] [Indexed: 12/12/2022]
Abstract
There is diversity in clinical outcome of Helicobacter pylori infection in different regions. Microbial, host and environmental factors seem to be reason of such variation. Considering microbial factors, we studied H. pylori genotypes and their association with clinical feature of the infection. Overall 160 H. pylori-positive patients were enrolled in this study. Clinical information and biopsy were collected from each patient. The presence of the major virulence genes were determined by PCR. Regardless to clinical outcomes, vacA, cagA, cagE, oipA, iceA1, babA2 and babB genes was positive in 100%, 69%, 51%, 55%, 26%,78% and 28% of 160 strains respectively. The s1m2 was more common vacA allels and s1a and m1a were predominant s and m regions. In patient with gastric cancer (GC), the oipA was less frequent while the iceA1 was the most common. The babA2 was common in all patient groups. The babB was significantly observed in strains isolated from patients with GC. There were significant association among cagA status with presence of vacAs1, vacAm2, cagE, oipA, iceA1 and babA2. Presence of the babB and oipA was connected with higher and lower risk for GC respectively. There was no association between the cagA, vacA, cagE or iceA status and clinical outcome in patients in Iran. We showed that presence of the babB and iceA1 were significantly connected with higher risk for gastric cancer development in Iranian dyspeptic patients while H. pylori isolates with positive oipA had little threat for leading patients to cancer.
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Affiliation(s)
- Hossein Dabiri
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Medical Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereshteh Jafari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Baghaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leila Shokrzadeh
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Abdi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohamad Amin Pourhoseingholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Mohammadzadeh
- Department of Microbiology, School of Medicine, Gonabad University of Medical Science, Gonabad, Iran
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17
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Chen YL, Mo XQ, Huang GR, Huang YQ, Xiao J, Zhao LJ, Wei HY, Liang Q. Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal diseases. World J Gastroenterol 2016; 22:9718-9726. [PMID: 27956795 PMCID: PMC5124976 DOI: 10.3748/wjg.v22.i44.9718] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 08/17/2016] [Accepted: 09/06/2016] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a kind of chronic infectious pathogen which can cause chronic gastritis, peptic ulcer, gastric cancer and other diseases. The genetic structure of the pathogenic genes of H. pylori varies largely, which contributes to the differences in virulence among various strains, and in clinical symptoms. Virulence genes of H. pylori can be categorized into three main classes: those related to adhesion and colonization, those related to gastric mucosal injury, and others. This review focuses on the relationship between genetic polymorphisms of the three classes of virulence genes of H. pylori and diseases. Most of the genetic polymorphisms of the main virulence factors of H. pylori are summarized in this paper.
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Kocazeybek B, Tokman HB. Prevalence of Primary Antimicrobial Resistance of H. pylori in Turkey: A Systematic Review. Helicobacter 2016; 21:251-260. [PMID: 26395982 DOI: 10.1111/hel.12272] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The prevalence of clarithromycin resistance has increased to the 20% or more in different regions of the world. Clarithromycin resistance is known to be responsible for most of the treatment failures in Helicobacter pylori (H. pylori) infection. The aim of this systematic review was to summarize the prevalence of primary antibiotic resistance (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline) of H. pylori strains in different geographical regions of Turkey. MATERIAL AND METHODS An Internet search was performed using PubMed and the ULAKBIM Turkish Medical Database. The terms "primary antibiotic resistance (separately; amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline) of H. pylori" with and without "Turkey" or "different geographical regions of Turkey" were searched among articles published in both English and Turkish language within the time span from 1999 to 2015. Data analysis was performed using MedCalc 12.7.0. Each article was weighted according to the number of isolated H. pylori strains. Pooled proportion analysis was performed. RESULTS Twenty-one Turkish studies including 1059 H. pylori strains were included in this review. The overall primary antibiotic resistance rates of H. pylori strains isolated in Turkey were as follows: amoxicillin 3 (0.971%), clarithromycin 425 (24.864%), metronidazole 75 (33.747%), tetracycline 2 (3.511%), and levofloxacin 31 (23.769%). CONCLUSIONS Primary antibiotic resistance against H. pylori in Turkey shows differences between geographical regions and population densities. There is an increase in primary resistance rates to clarithromycin and metronidazole in different years. The data are not sufficient for tetracycline, amoxicillin, and levofloxacin. High clarithromycin resistance rates were mostly detected in overpopulated cities like Ankara (north), Izmir (west), Istanbul (west), and Bursa (west).
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Affiliation(s)
- Bekir Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Li N, Xie C, Lu NH. Transforming growth factor-β: an important mediator in Helicobacter pylori-associated pathogenesis. Front Cell Infect Microbiol 2015; 5:77. [PMID: 26583078 PMCID: PMC4632021 DOI: 10.3389/fcimb.2015.00077] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 10/20/2015] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (H.pylori) is a Gram-negative, microaerophilic, helical bacillus that specifically colonizes the gastric mucosa. The interaction of virulence factors, host genetic factors, and environmental factors contributes to the pathogenesis of H. pylori-associated conditions, such as atrophic gastritis and intestinal metaplasia. Infection with H. pylori has recently been recognized as the strongest risk factor for gastric cancer. As a pleiotropic cytokine, transforming growth factor (TGF)-β regulates various biological processes, including cell cycle, proliferation, apoptosis, and metastasis. Recent studies have shed new light on the involvement of TGF-β signaling in the pathogenesis of H. pylori infection. This review focuses on the potential etiological roles of TGF-β in H. pylori-mediated gastric pathogenesis.
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Affiliation(s)
- Nianshuang Li
- Department of Gastroenterology, Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Chuan Xie
- Department of Gastroenterology, Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Nong-Hua Lu
- Department of Gastroenterology, Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University Nanchang, China
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20
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da Costa DM, Pereira EDS, Rabenhorst SHB. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases. World J Gastroenterol 2015; 21:10563-72. [PMID: 26457016 PMCID: PMC4588078 DOI: 10.3748/wjg.v21.i37.10563] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/13/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature.
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Prevalence of Helicobacter pylori vacA, cagA, and iceA Genotypes in Cuban Patients with Upper Gastrointestinal Diseases. BIOMED RESEARCH INTERNATIONAL 2015; 2015:753710. [PMID: 25945344 PMCID: PMC4402555 DOI: 10.1155/2015/753710] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 01/23/2015] [Accepted: 01/29/2015] [Indexed: 02/06/2023]
Abstract
Virulence factors of Helicobacter pylori can predict the development of different gastroduodenal diseases. There are scarce reports in Cuba about H. pylori isolates genotyping. The aim of the present investigation was to identify allelic variation of the virulence genes vacA, cagA, and iceA in sixty-eight patients diagnosed as H. pylori positive by culture. In seven out of 68 patients, strains from both gastric regions were obtained and considered independent. DNA was extracted from all the H. pylori strains and evaluated by PCR-genotyping. The vacA s1 allele, cagA gene, and iceA2 allele were the most prevalent (72.0%, 56.0%, and 57.3%, respectively). Alleles from m-region showed a similar frequency as s1a and s1b subtypes. The presence of multiple H. pylori genotypes in a single biopsy and two gastric region specimens were found. Significant statistical association was observed between iceA2 allele and patients with non-peptic ulcer dyspepsia (NUD) (P = 0.037) as well as virulence genotypes (s1, s1m2) and patients over 40 years old (P < 0.05). In conclusion, the results demonstrated a high prevalence of H. pylori virulent genotypes in Cuban patients over 40 years old while iceA2 alleles demonstrated a good specificity in patients with NUD.
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22
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Almeida N, Donato MM, Romãozinho JM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Fernandes A, Sofia C. Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country. Dig Dis Sci 2015; 60:74-85. [PMID: 25142169 DOI: 10.1007/s10620-014-3319-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 08/01/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. AIM This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included. RESULTS Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b-19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1-18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2-66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 + cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. CONCLUSIONS cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagA-positive strains are correlated with more severe histopathological modifications. This gene is commonly associated with vacA s1m1, and such isolates are frequently found in patients with peptic ulcer.
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Affiliation(s)
- Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital Centre, Praceta Mota Pinto e Avenida Bissaya Barreto, 3000-075, Coimbra, Portugal,
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Homan M, Šterbenc A, Kocjan BJ, Luzar B, Zidar N, Orel R, Poljak M. Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree of gastritis in infected Slovenian children. Antonie Van Leeuwenhoek 2014; 106:637-645. [PMID: 25055876 DOI: 10.1007/s10482-014-0234-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/07/2014] [Indexed: 12/16/2022]
Abstract
The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9% of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.
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Affiliation(s)
- Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, Ljubljana, Slovenia,
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Virulence factors and antibiotic resistance in children with Helicobacter pylori gastritis. J Pediatr Gastroenterol Nutr 2014; 58:608-12. [PMID: 24792628 DOI: 10.1097/mpg.0000000000000273] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES There are limited data regarding the pattern of Helicobacter pylori (Hp) antibiotic resistance and virulence factors in children. Evaluation of prevalence of drug resistance and virulence-factor genotype in children with Hp gastritis and to investigate whether there is any relation between drug resistance and genotype were our aims in this study. METHODS Ninety-eight children with polymerase chain reaction-positive Hp gastritis were included. Antimicrobial susceptibility was tested by disc diffusion method and polymerase chain reaction assays were used for the determination of virulence factors. RESULTS The resistance rates to clarithromycin, metronidazole, and amoxicillin were 23.5%, 11.7%, and 3.9%, respectively. All strains carried vacA genotype, and 51%, 70.4%, 49%, 34.7%, and 25.5% were cagA-, cagE-, babA2-, iceA1-, and iceA2-positive, respectively. Of those 98 specimens, 81.6%, 19.4%, 38.8%, and 63.3% carried vacAs1, vacAs2, vacAm1, and vacAm2, respectively. Dominant vacA type was s1am2 (32.7%), followed by s1am1 (14.3%) and s2m2 (12.2%). Significant rates of clarithromycin resistance were observed in cagE-, iceA1-, babA2-, and vacAs1c-positive groups. In those with metronidazole resistance, vacAs1 and vacAs1c were more common (P < 0.05). CONCLUSIONS The cagE-positive and vacA s1a/m2 genotypes, which are correlated with increased antibiotic resistance, were predominant in our population. In countries where Hp infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.
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Ramis IB, Vianna JS, Silva Junior LVD, Von Groll A, Silva PEAD. cagE as a biomarker of the pathogenicity of Helicobacter pylori. Rev Soc Bras Med Trop 2013; 46:185-9. [PMID: 23740068 DOI: 10.1590/0037-8682-0054-2012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Accepted: 02/07/2013] [Indexed: 01/01/2023] Open
Abstract
INTRODUCTION Helicobacter pylori infection is associated with gastro-duodenal diseases. Genes related to pathogenicity have been described for H. pylori and some of them appear to be associated with more severe clinical outcomes of the infection. The present study investigates the role of cagE as a pathogenicity biomarker of H. pylori compare it to cagA, vacA, iceA and babA2 genes and correlate with endoscopic diagnoses. METHODS Were collected biopsy samples of 144 dyspeptic patients at the Hospital of the Federal University of Rio Grande, Rio Grande do Sul, Brazil. After collection, the samples were sent for histological examination, DNA extraction and detection of all putative pathogenicity genes by PCR. RESULTS Of the 144 patients undergoing endoscopy, 57 (39.6%) presented H. pylori by histological examination and PCR by detection of the ureA gene. Based on the endoscopic diagnoses, 45.6% (26/57) of the patients had erosive gastritis, while 54.4% (31/57) had enanthematous gastritis. The genes cagA, cagE, vacAs1/m1, vacAs1/m2 and iceA1 were related to erosive gastritis, while the genes vacAs2/m2, iceA2 and babA2 were associated to enanthematous gastritis. We found a statistically significant association between the presence of cagE and the endoscopic diagnosis. However, we detect no statistically significant association between the endoscopic diagnosis and the presence of cagA, vacA, iceA and babA2, although a biological association has been suggested. Conclusions Thus, cagE could be a risk biomarker for gastric lesions and may contribute to a better evaluation of the H. pylori pathogenic potential and to the prognosis of infection evolution in the gastric mucosa.
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Affiliation(s)
- Ivy Bastos Ramis
- Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, RS, Brasil
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Boyanova L, Panov V, Yordanov D, Gergova G, Mitov I. Characterization of oral Helicobacter pylori strain by 4 methods. Diagn Microbiol Infect Dis 2013; 77:287-8. [PMID: 24075629 DOI: 10.1016/j.diagmicrobio.2013.06.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Revised: 06/13/2013] [Accepted: 06/23/2013] [Indexed: 12/18/2022]
Abstract
The aim of the study was to describe oral Helicobacter pylori strain from a child by 4 methods. The strain was positive by immunofluorescence, ureA- and cagA positive, vacA s1 m2 genotype and resistant to metronidazole and clarithromycin. In conclusion, virulent and antibiotic resistant H. pylori strains can be present in oral cavity from patients with chronic dental and gastroduodenal diseases.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria.
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Buzás GM. [Helicobacter pylori - 2012]. Orv Hetil 2012; 153:1407-18. [PMID: 22951408 DOI: 10.1556/oh.2012.29443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The author overviews some aspects of literature data of the past 2 years. Genetic research has identified polymorphisms of Helicobacter pylori virulence factors and the host which could play a role in the clinical outcome of the infection (peptic ulcer or gastric cancer). So far they have been performed in research centers but with a decrease of costs, they will take their place in diagnosing the diseases and tailoring the treatment. Antibiotic resistance is still growing in Southern European countries and is decreasing in Belgium and Scandinavia. Currently, the clarithromycin resistance rate is of 17-33% in Budapest and levofloxacin resistance achieved 27%. With careful assessment of former antibiotic use the resistance to certain antibiotics can be avoided and the rates of eradication improved. Immigration is a growing problem worldwide: according to Australian, Canadian and Texan studies, the prevalence of Helicobacter pylori is much higher in the immigrant groups than in the local population. An Italian study showed that the eradication rate of triple therapy is significantly lower in the Eastern European immigrants than in the Italians. A recent research has suggested a link between female/male infertility, habitual abortion and Helicobacter pylori infection. However, there are no published data or personal experience to show whether successful eradication of the virus in these cases is followed by successful pregnancies or not. The author overviews the Maastricht process and analyzes the provisions of the Maastricht IV/Florence consensus, in which the new diagnostic algorithms and indications of eradication therapy are reformulated according to the latest levels of evidence and recommendation grading. According to the "test and treat" strategy, either the urea breath test or the stool monoclonal antigen test are recommended as a non-invasive diagnostic method in primary care. Endoscopy is still recommended in case of alarm symptoms, complicated ulcer, or if there is a suspicion of malignancy or MALT lymphoma. Local resistance to clarithromycin and levofloxacin should be considered in the choice of first-line therapy, in case of levels >15-20% these compounds should not be used. In regions with low resistance rates, classical triple therapy remains the regimen of choice; its alternative is the bismuth-based quadruple therapy. Determining antimicrobial resistance is justified after failed second- or third-line therapies; where available, molecular methods (fluorescence in situ hybridization, polymerase chain reaction) should be used. As second/third line treatments, the sequential, bismuth-based quadruple, concomitant quadruple regimens, hybrid are all possible alternatives. The Hungarian diagnostic and therapeutic approach in practice is different in some aspects from the provisions of the European consensus. Orv. Hetil., 2012, 153, 1407-1418.
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Affiliation(s)
- György Miklós Buzás
- Ferencvárosi Egészségügyi Szolgáltató Kiemelkedően Közhasznú Nonprofit Kft. Gasztroenterológiai szakrendelés Budapest.
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Yordanov D, Boyanova L, Markovska R, Gergova G, Mitov I. Significance of Helicobacter pylori vacA intermediate region genotyping-a Bulgarian study. Diagn Microbiol Infect Dis 2012; 74:253-7. [PMID: 22951332 DOI: 10.1016/j.diagmicrobio.2012.07.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2012] [Revised: 07/18/2012] [Accepted: 07/19/2012] [Indexed: 01/25/2023]
Abstract
The significance of the intermediate (i) region of the Helicobacter pylori vacA gene as a virulence factor associated with the severity of gastric disease is still disputable. The aim of the present study was to evaluate the prevalence and significance of vacA i alleles alone or in combination with other vacA alleles in symptomatic Bulgarian patients and to find out possible associations between vacA i genotype and patients' disease, age, sex, and other H. pylori virulence factors. Unlike vacA s1 and m1, vacA i1 prevalence was significantly higher (75.0%) in strains from peptic ulcer patients than in strains from nonulcer patients with gastric diseases (58.6%) (P = 0.022). Less virulent vacA s1 i2 m2 strains were more prevalent in females (P = 0.03), and cagA(+) was associated with vacA i1, s1, m1, and their combinations. In conclusion, vacA i status is a better predictor for the strain virulence than other vacA alleles.
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Affiliation(s)
- Daniel Yordanov
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria.
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Boyanova L. Role of Helicobacter pylori virulence factors for iron acquisition from gastric epithelial cells of the host and impact on bacterial colonization. Future Microbiol 2011; 6:843-6. [PMID: 21861616 DOI: 10.2217/fmb.11.75] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
EVALUATION OF: Tan S, Noto JM, Romero-Gallo J, Peek RM Jr, Amieva MR. Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface. PLoS Pathog. 7(5), E1002050 (2011). The effects of Helicobacter pylori virulence factors on gastric epithelial cells are topics open to many studies. Major virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin (VacA), predict severe infection outcomes in many countries. H. pylori possesses various proteins for iron transport/storage, however, mechanisms of iron acquisition are not fully evaluated. The study by Tan et al. reveals a concurrent CagA/VacA activity for micronutrient acquisition and host tissue colonization. The virulence factors possess new activities, involving VacA-induced apical mislocalization of transferrin receptors to regions of H. pylori attachment and effects of both factors on polarized uptake and recycling of transferrin. The authors used many in vitro methods and an animal model. Iron acquisition by CagA was proven in vitro and in vivo by strain colonization of the gastric mucosa in iron-depleted conditions. CagA EPIYA motifs were associated with increased host internalization of transferrin. Importantly, CagA and VacA were involved in iron acquisition and colonization without severely damaging the host cells, thus favoring the infection chronicity. Further studies should assess molecular mechanisms of H. pylori iron acquisition, comparative activities of contact-dependent/soluble VacA and Eastern/Western CagA on the polarized epithelium and long-term effects of iron deficiency by virulent versus less virulent H. pylori strains. An interesting topic is the association of virulent strains with iron deficiency anemia but also with various H. pylori-induced diseases, in different populations and, possibly, for other bacterial infections. In conclusion, H. pylori iron acquisition is multifaceted. CagA and VacA work concurrently to provide both iron acquisition from interstitial holotransferrin and enhanced bacterial colonization of host cells apically. The new activities of the major virulence factors of adherent H. pylori are important both to research and in a clinical setting.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, Bulgaria.
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Benefits of Helicobacter pylori cagE genotyping in addition to cagA genotyping: a Bulgarian study. Antonie van Leeuwenhoek 2011; 100:529-35. [PMID: 21701821 DOI: 10.1007/s10482-011-9608-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2011] [Accepted: 06/07/2011] [Indexed: 01/16/2023]
Abstract
Associations of Helicobacter pylori cagE status with complex patient characteristics remain to be elucidated in Eastern Europe. The aim of this study was to assess the frequencies of cagE gene and cagA/cagE combinations in H. pylori strains from symptomatic Bulgarian patients and to improve cagA detection. cagA and cagE genotypes were evaluated in 219 patients with single-strain infections. In total, 84.9% of strains were cagA (+), while 68.5% were cagE (+). cagA (+), cagE (+), and cagA (+)/cagE (+) strains were more prevalent in peptic ulcer (93.8%, 84.4%, and 84.4%) compared with nonulcer patients (81.3%, 61.9%, and 61.3%, respectively). In elderly patients, cagE (+) and cagA (+)/cagE (+) strains were 1.9-fold more common than in the 12 children evaluated. Only 10% of the elderly subjects harbored low-virulence cagA (+)/cagE (-) strains compared with 16.8% of adults and 41.7% of children. Intriguingly, prevalence of the cagA (+)/cagE (-) genotype was 2.1-fold lower in men than in women, suggesting a higher frequency of more virulent strains in men. The presence of both cag genes and combinations was not linked to strain susceptibility to clarithromycin or metronidazole, place of residence, or prior therapy. Use of an extra primer pair increased cagA detection in 14.7% of 31 cagA (-) strains. In conclusion, use of a second primer pair for the cagA gene can be recommended in countries with common cagA (+) strains. Although both cag genes were linked to severe diseases in Bulgarian patients, the best discrimination of virulent strains was obtained by the cagA/cagE combination or by the cagE gene alone. cagE prevalence increased gradually with patient age, while the cagA (+)/cagE (-) genotype, implying a disrupted cag pathogenicity island, was associated with both younger age and female gender.
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