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2 results on '"Pylori cagA-positive Strains"'

1. Evaluating the origin and virulence of a Helicobacter pylori cagA-positive strain isolated from a non-human primate

Author

Kana Hashi, Chihiro Imai, Koji Yahara, Kamrunnesa Tahmina, Takeru Hayashi, Takeshi Azuma, Takako Miyabe-Nishiwaki, Hideyuki Sato, Masao Matsuoka, Sachi Niimi, Munehiro Okamoto, and Masanori Hatakeyama

Subjects
Pylori cagA-positive Strains, Western CagA, Organoid, CagA Protein, East Asian CagA, Medicine, Science
Abstract

Abstract Helicobacter pylori cagA-positive strains are critically involved in the development of gastric cancer. Upon delivery into gastric epithelial cells via type IV secretion, the cagA-encoded CagA interacts with and thereby perturbs the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1b via the tyrosine-phosphorylated EPIYA-C/D segment and the CM sequence, respectively. Importantly, sequences spanning these binding regions exhibit variations among CagA proteins, which influence the pathobiological/oncogenic potential of individual CagA. Here we isolated an H. pylori strain (Hp_TH2099) naturally infecting the stomach of a housed macaque, indicating a zoonotic feature of H. pylori infection. Whole genome sequence analysis revealed that Hp_TH2099 belongs to the hpAsia2 cluster and possesses ABC-type Western CagA, which contains hitherto unreported variations in both EPIYA-C and CM sequences. The CM variations almost totally abolished PAR1b binding. Whereas pTyr + 5 variation in the EPIYA-C segment potentiated SHP2-binding affinity, pTyr-2 variation dampened CagA tyrosine phosphorylation and thus impeded CagA-SHP2 complex formation. As opposed to the H. pylori standard strain, infection of mouse ES cell-derived gastric organoids with Hp_TH2099 failed to elicit CagA-dependent epithelial destruction. Thus, the macaque-isolated H. pylori showed low virulence due to attenuated CagA activity through multiple substitutions in the sequences involved in binding with SHP2 and PAR1b.

Published
2018
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2. Evaluating the origin and virulence of a Helicobacter pylori cagA-positive strain isolated from a non-human primate

Author

Sachi Niimi, Kamrunnesa Tahmina, Takako Miyabe-Nishiwaki, Munehiro Okamoto, Hideyuki Sato, Masao Matsuoka, Kana Hashi, Takeshi Azuma, Koji Yahara, Masanori Hatakeyama, Takeru Hayashi, and Chihiro Imai

Subjects
0301 basic medicine, Organoid, Models, Molecular, Bacterial toxins, Protein Conformation, Cell Cycle Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein tyrosine phosphatase, Mice, Zoonoses, Protein Interaction Mapping, CagA Protein, Peptide sequence, Multidisciplinary, Gastric Juice, biology, Virulence, Bacterial host response, Recombinant Proteins, Organoids, Pylori cagA-positive Strains, Phenotype, Medicine, Pathogens, Science, Sequence alignment, Protein Serine-Threonine Kinases, Western CagA, Article, Helicobacter Infections, 03 medical and health sciences, Bacterial Proteins, Species Specificity, CagA, Animals, Humans, Secretion, Amino Acid Sequence, Cellular microbiology, Gene, Antigens, Bacterial, Binding Sites, Helicobacter pylori, Sequence Homology, Amino Acid, Bacterial pathogenesis, biology.organism_classification, bacterial infections and mycoses, Molecular biology, digestive system diseases, East Asian CagA, 030104 developmental biology, Genes, Bacterial, Macaca, bacteria, Sequence Alignment
Abstract

Helicobacter pylori cagA-positive strains are critically involved in the development of gastric cancer. Upon delivery into gastric epithelial cells via type IV secretion, the cagA-encoded CagA interacts with and thereby perturbs the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1b via the tyrosine-phosphorylated EPIYA-C/D segment and the CM sequence, respectively. Importantly, sequences spanning these binding regions exhibit variations among CagA proteins, which influence the pathobiological/oncogenic potential of individual CagA. Here we isolated an H. pylori strain (Hp_TH2099) naturally infecting the stomach of a housed macaque, indicating a zoonotic feature of H. pylori infection. Whole genome sequence analysis revealed that Hp_TH2099 belongs to the hpAsia2 cluster and possesses ABC-type Western CagA, which contains hitherto unreported variations in both EPIYA-C and CM sequences. The CM variations almost totally abolished PAR1b binding. Whereas pTyr + 5 variation in the EPIYA-C segment potentiated SHP2-binding affinity, pTyr-2 variation dampened CagA tyrosine phosphorylation and thus impeded CagA-SHP2 complex formation. As opposed to the H. pylori standard strain, infection of mouse ES cell-derived gastric organoids with Hp_TH2099 failed to elicit CagA-dependent epithelial destruction. Thus, the macaque-isolated H. pylori showed low virulence due to attenuated CagA activity through multiple substitutions in the sequences involved in binding with SHP2 and PAR1b.

Published
2018

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