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

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 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.

Diagnostic reliability of nested PCR depends on the primer design and threshold abundance ofHelicobacter pyloriin biopsy, stool, and saliva samples

“…In one case the stomach contained a mixture of two strains, however, the saliva contained only a single strain from this mixture (Table S1, sample 24). Different strains in stomach and saliva were found in the two other patients (Table S1; samples 23,60). Furthermore, in three of eight positive samples, H pylori was found exclusively in saliva/oral cavity and was not identified by any other method.…”

“…All samples were stored in the freezer at −20°C. A culture of H pylori J493 with partial 16S rRNA sequence identical to clinical isolate B128 used in optimizing and spiking experiments was provided by Dr Silvia Vašková Laboratories Piešťany, sro. Slovakia.…”

Whole Genome Sequencing Reveals Virulence Potentials of Helicobacter pylori Strain KE21 Isolated from a Kenyan Patient with Gastric Signet Ring Cell Carcinoma

“…However, this KE21 ICEH ptfs 4 cannot be assigned to any of the known subtypes ( Supplementary Materials, Table S4 ) [ 23 ]. The second genomic island had 47 predicted CDS that were inserted within a chromosomal region of 49,454 bp (coordinates: 706,360-755,813 in genome sequence) located between genes encoding the 4-hydroxy-tetrahydrodipicolinate reductase ( dapB ) and the glutamate racemase ( glr ), a region known as dg-region [ 25 ]. Remarkably, this dg-region encoded a cluster of cytotoxin-associated genes known as cag pathogenicity island (cagPAI) ( Supplementary Materials, Table S5 ).…”

Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function

“…Three genome islands, all of which encode complete or partial T4SSs, have been described in H. pylori . The 40 kb cag pathogenicity island is integrated at a specific genome locus and flanked by direct 31 bp repeats ( Censini et al, 1996 ), but may be rearranged in some strains ( Fischer, 2011 ; Su et al, 2019 ). It encodes the Cag T4SS and its effector protein, the cytotoxin-associated antigen CagA, both of which are well-known as major H. pylori virulence factors.…”