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

Scientific Reports
Hanfu SuJeong-Heon Cha

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 ...Continue Reading

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Datasets Mentioned

BETA
PRJNA419269
MK089812
MK089815

Methods Mentioned

BETA
PCR
PCRs
genotyping
protein assay
electrophoresis
X-ray

Software Mentioned

SMRT Analysis
Multi Locus Sequence Typing ( MLST )
Mega
PacBio
BLAST
BLAST Ratios EDGAR
CLgenomics
MGR
progressiveMauve
PHYLIP

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