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

• Published in: Scientific reports 2019-08, Vol.9 (1), p.11203-13, Article 11203
• Main Authors: Su, Hanfu, Tissera, Kavinda, Jang, Sungil, Choi, Yun Hui, Kim, Aeryun, Cho, Yong-Joon, Li, Meiling, Gunawardhana, Niluka, Merrell, D. Scott, Ge, Linhu, Cha, Jeong-Heon
• Format: Article
• Language: English
• Subjects: 45; 631/208/464; 631/326/325/2482; 631/326/41/2530; 631/326/41/2531; 631/326/421; Antigens, Bacterial - genetics; Bacterial Proteins - genetics; Biological Coevolution; Contraction; Copy number; DNA Copy Number Variations; DNA, Intergenic - genetics; Evolution, Molecular; Gastric cancer; Gene Duplication; Genes, Bacterial - genetics; Genomic analysis; Genomics; Genotype & phenotype; Genotypes; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Host Microbial Interactions - genetics; Humanities and Social Sciences; Humans; Molecular Typing; multidisciplinary; Science; Science (multidisciplinary); Strains (organisms); Virulence - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-47240-2

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 cag PAI appears to have been independently introduced into two different H . pylori types, termed pre-type-A and pre-type-B, which consequently evolved to cag PAI type-A and type-B, respectively; importantly, all multi- cagA genotype strains displayed cag PAI 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  cag PAI type-B). Furthermore, introduction of this genetic element into strain G27 (hpEurope/type-A and  cag PAI 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 cag PAI 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.