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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 
 Scientific Reports, Vol.9(1) : 11203, 2019 
Journal Title
 Scientific Reports 
Issue Date
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
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