Evolutionary mechanism leading to the multi-cagA genotype in Helicobacter pylori

Hanfu Su, Kavinda Tissera, Sungil Jang, Yun Hui Choi, Aeryun Kim, Yong Joon Cho, Meiling Li, Niluka Gunawardhana, D. Scott Merrell, Linhu Ge, Jeong Heon Cha

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Abstract

Infection with CagA+ Helicobacter pylori strains is linked to an increased risk for gastric diseases, including gastric cancer. Recent evidence indicates that dynamic expansion and contraction of cagA copy number may serve as a novel mechanism to enhance disease development. Herein, comparative genomic analysis divided hpEurope into two groups: hpEurope/type-A and type-B. Only hpEurope/type-B displayed the multi-cagA genotype. Further analysis showed that cagPAI appears to have been independently introduced into two different H. pylori types, termed pre-type-A and pre-type-B, which consequently evolved to cagPAI type-A and type-B, respectively; importantly, all multi-cagA genotype strains displayed cagPAI type-B. Two direct cagA-flanking repeats of a genetic element termed CHA-ud were essential for the multi-cagA genotype in strain PMSS1 (hpEurope/type-B and cagPAI type-B). Furthermore, introduction of this genetic element into strain G27 (hpEurope/type-A and cagPAI type-A) was sufficient to generate the multi-cagA genotype. The critical steps in the evolution of the multi-cagA genotype involved creation of CHA-ud at cagA upstream in cagPAI type-B strains followed by its duplication to cagA downstream. En masse, elucidation of the mechanism by which H. pylori evolved to carry multiple copies of cagA helps to provide a better understanding of how this ancient pathogen interacts with its host.

Original languageEnglish
Article number11203
Pages (from-to)11203
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Aug 1

All Science Journal Classification (ASJC) codes

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    Su, H., Tissera, K., Jang, S., Choi, Y. H., Kim, A., Cho, Y. J., Li, M., Gunawardhana, N., Merrell, D. S., Ge, L., & Cha, J. H. (2019). Evolutionary mechanism leading to the multi-cagA genotype in Helicobacter pylori. Scientific reports, 9(1), 11203. [11203]. https://doi.org/10.1038/s41598-019-47240-2