Helicobacter pylori Antimicrobial Resistance and Gene Variants in High- and Low-Gastric-Cancer-Risk Populations

ABSTRACT Colombia, South America has one of the world’s highest burdens of Helicobacter pylori infection and gastric cancer. While multidrug antibiotic regimens can effectively eradicate H. pylori, treatment efficacy is being jeopardized by the emergence of antibiotic-resistant H. pylori strains. Moreover, the spectrum of and genetic mechanisms for antibiotic resistance in Colombia is underreported. In this study, 28 H. pylori strains isolated from gastric biopsy specimens from a high-gastric-cancer-risk (HGCR) population living in the Andes Mountains in Túquerres, Colombia and 31 strains from a low-gastric-cancer-risk (LGCR) population residing on the Pacific coast in Tumaco, Colombia were subjected to antibiotic susceptibility testing for amoxicillin, clarithromycin, levofloxacin, metronidazole, rifampin, and tetracycline. Resistance-associated genes were amplified by PCR for all isolates, and 29 isolates were whole-genome sequenced (WGS). No strains were resistant to amoxicillin, clarithromycin, or rifampin. One strain was resistant to tetracycline and had an A926G mutation in its 16S rRNA gene. Levofloxacin resistance was observed in 12/59 isolates and was significantly associated with N87I/K and/or D91G/Y mutations in gyrA. Most isolates were resistant to metronidazole; this resistance was significantly higher in the LGCR (31/31) group compared to the HGCR (24/28) group. Truncations in rdxA and frxA were present in nearly all metronidazole-resistant strains. There was no association between phylogenetic relationship and resistance profiles based on WGS analysis. Our results indicate H. pylori isolates from Colombians exhibit multidrug antibiotic resistance. Continued surveillance of H. pylori antibiotic resistance in Colombia is warranted in order to establish appropriate eradication treatment regimens for this population.

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Helicobacter pylori Infection and Gastric Cancer Risk: Evaluation of 15 H. pylori Proteins Determined by Novel Multiplex Serology

Cancer Research ◽

10.1158/0008-5472.can-09-0596 ◽

2009 ◽

Vol 69 (15) ◽

pp. 6164-6170 ◽

Cited By ~ 58

Author(s):

Lei Gao ◽

Angelika Michel ◽

Melanie N. Weck ◽

Volker Arndt ◽

Michael Pawlita ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Risk Evaluation ◽

Helicobacter Pylori Infection ◽

Gastric Cancer Risk ◽

H Pylori ◽

Multiplex Serology

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Phylogeographic Origin of Helicobacter pylori Determines Host-Adaptive Responses upon Coculture with Gastric Epithelial Cells

Infection and Immunity ◽

10.1128/iai.01182-12 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2468-2477 ◽

Cited By ~ 16

Author(s):

Alexander Sheh ◽

Rupesh Chaturvedi ◽

D. Scott Merrell ◽

Pelayo Correa ◽

Keith T. Wilson ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Gastric Disease ◽

Gastric Epithelial Cells ◽

Gastric Cancer Risk ◽

Content Type ◽

H Pylori ◽

Induced Apoptosis

ABSTRACTWhileHelicobacter pyloriinfects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors inH. pyloripathogenesis, global gene expression of sixH. pyloriisolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factorscagA,vacA, andbabBand were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin ofH. pyloristrains may promote increased gastric disease.

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Faculty Opinions recommendation of Helicobacter pylori infection and gastric cancer risk: evaluation of 15 H. pylori proteins determined by novel multiplex serology.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1164301.626017 ◽

2009 ◽

Author(s):

Steven Moss

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Risk Evaluation ◽

Helicobacter Pylori Infection ◽

Gastric Cancer Risk ◽

H Pylori ◽

Multiplex Serology

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Antimicrobial Susceptibility and Resistance Patterns among Helicobacter pylori Strains from The Gambia, West Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00517-12 ◽

2012 ◽

Vol 57 (3) ◽

pp. 1231-1237 ◽

Cited By ~ 35

Author(s):

Ousman Secka ◽

Douglas E. Berg ◽

Martin Antonio ◽

Tumani Corrah ◽

Mary Tapgun ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Susceptibility ◽

Respiratory Infections ◽

Gene Mutations ◽

Tetracycline Resistance ◽

The Gambia ◽

Rrna Gene ◽

Content Type ◽

H Pylori ◽

Few Data

ABSTRACTHelicobacter pyloriis a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four GambianH. pyloristrains were tested for antibiotic susceptibility. The role ofrdxAin metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P= 0.0031). Representative Mtz-resistant (Mtzr) strains were rendered Mtz susceptible (Mtzs) by transformation with a functionalrdxAgene; conversely, Mtzsstrains were rendered MtzrbyrdxAinactivation. Many mutations were found by GambianH. pylorirdxAsequencing; mutations that probably inactivatedrdxAin Mtzrstrains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety ofrdxAmutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.

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Histopathology of Helicobacter pylori associated gastritis in children from high-and low-gastric cancer risk populations

Gastroenterology ◽

10.1016/s0016-5085(01)83269-8 ◽

2001 ◽

Vol 120 (5) ◽

pp. A657-A657

Author(s):

A BEDOYA ◽

J GARAY ◽

F SANZON ◽

J BRAVO ◽

H CORREA ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Gastric Cancer Risk

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Faculty Opinions recommendation of Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717965373.793466434 ◽

2012 ◽

Author(s):

Silvia Franceschi ◽

Jean-Damien Combes ◽

Catherine de Martel

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Prospective Study ◽

Helicobacter Pylori Infection ◽

Gastric Cancer Risk ◽

A Prospective Study

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Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

International Journal of Veterinary Science ◽

10.37422/ijvs/20.043 ◽

2020 ◽

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Helicobacter Pylori ◽

Cancer Stem Cells ◽

Histopathological Examination ◽

Physiological Saline ◽

Rrna Gene ◽

Peptic Ulcers ◽

Gastric Cancer Stem Cells ◽

H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

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