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Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients.

ABSTRACT: Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Tyr-Ala (EPIYA) segments) and vacA genotypes (s and m regions) were determined using PCR-based sequencing and PCR, respectively. In total, 368 patients were examined (341 gastritis, 10 peptic ulcer, and 17 gastric cancer). Sixty-two (16.8%) strains were cagA-negative and 306 (83.1%) were cagA-positive (293 Western-type, 12 East-Asian-type, and one hybrid type). All cagA-negative strains were isolated from gastritis patients. In the gastritis group, 78.6% (268/341) had Western-type CagA, 2.9% (10/341) had East-Asian-type, and 18.2% (61/341) were cagA-negative. However, all H. pylori from gastric cancer patients possessed Western-type CagA. Histological analyses showed that East-Asian-type CagA was the most virulent strains, followed by Western-type and cagA-negative strains. This finding agreed with the current consensus. CagA-positive strains were the most virulent type. However, the fact that different CagA types can explain the high incidence of gastric cancer might be inapplicable in Mongolia.

SUBMITTER: Tserentogtokh T

PROVIDER: S-EPMC6562502 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients.

Tserentogtokh Tegshee T Gantuya Boldbaatar B Subsomwong Phawinee P Oyuntsetseg Khasag K Bolor Dashdorj D Erdene-Ochir Yansan Y Azzaya Dashdorj D Davaadorj Duger D Uchida Tomohisa T Matsuhisa Takeshi T Yamaoka Yoshio Y

Cancers 20190524 5

Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Ty ...[more]

PMID: 31137742

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Project description:The clinical outcome of Helicobacter pylori infections is determined by multiple host-pathogen interactions that may develop to chronic gastritis, and sometimes peptic ulcers or gastric cancer. Highly virulent strains encode a type IV secretion system (T4SS) that delivers the effector protein CagA into gastric epithelial cells. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-sequence motifs, called A, B and C in Western-type strains, by members of the oncogenic Src and Abl host kinases. Phosphorylated EPIYA-motifs mediate interactions of CagA with host signaling factors--in particular various SH2-domain containing human proteins--thereby hijacking multiple downstream signaling cascades. Observations of tyrosine-phosphorylated CagA are mainly based on the use of commercial phosphotyrosine antibodies, which originally were selected to detect phosphotyrosines in mammalian proteins. Systematic studies of phosphorylated EPIYA-motif detection by the different antibodies would be very useful, but are not yet available. To address this issue, we synthesized phospho- and non-phosphopeptides representing each predominant Western CagA EPIYA-motif, and determined the recognition patterns of seven different phosphotyrosine antibodies in Western blots, and also performed infection studies with diverse representative Western H. pylori strains. Our results show that a total of 9-11 amino acids containing the phosphorylated EPIYA-motifs are necessary and sufficient for specific detection by these antibodies, but revealed great variability in sequence recognition. Three of the antibodies recognized phosphorylated EPIYA-motifs A, B and C similarly well; whereas preferential binding to phosphorylated motif A and motifs A and C was found with two and one antibodies, respectively, and the seventh anti-phosphotyrosine antibody did not recognize any phosphorylated EPIYA-motif. Controls showed that none of the antibodies recognized the corresponding non-phospho CagA peptides, and that all of them recognized phosphotyrosines in mammalian proteins. These data are valuable in judicious application of commercial anti-phosphotyrosine antibodies and in characterization of CagA phosphorylation during infection and disease development.

Dataset Information

Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients.

Publications

Western-Type <i>Helicobacter pylori</i> CagA are the Most Frequent Type in Mongolian Patients.

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