TY - JOUR
T1 - Evolutionary mechanism leading to the multi-cagA genotype in Helicobacter pylori
AU - Su, Hanfu
AU - Tissera, Kavinda
AU - Jang, Sungil
AU - Choi, Yun Hui
AU - Kim, Aeryun
AU - Cho, Yong Joon
AU - Li, Meiling
AU - Gunawardhana, Niluka
AU - Merrell, D. Scott
AU - Ge, Linhu
AU - Cha, Jeong Heon
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071011998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071011998&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-47240-2
DO - 10.1038/s41598-019-47240-2
M3 - Article
C2 - 31371778
AN - SCOPUS:85071011998
SN - 2045-2322
VL - 9
SP - 11203
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -
