Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin

Abstract

Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coexpressed with the vacuolating cytotoxin (VacA), a protein that causes ulceration in the stomach of mice. However, the relationship between these two virulence factors is unknown. To define whether CagA and VacA are coexpressed in all clinical isolates and their relationships, we collected 43 clinical isolates of H. pylori and studied their genetic and phenotypic properties. Based on this analysis, most of the strains could be classified into two major types. Type I bacteria had the gene coding for CagA and expressed the CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the gene coding for CagA and did not express either the CagA protein or the vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%, respectively, of the 43 clinical isolates, while the remaining 28% had an intermediate phenotype, expressing CagA independently of VacA or vice versa. This finding shows that although it is present in most cytotoxic strains, CagA is not necessary for the expression of the vacuolating cytotoxin.

The chemokine receptor CCR7 is expressed on epithelium of non-inflamed gastric mucosa, Helicobacter pylori gastritis, gastric carcinoma and its precursor lesions and up-regulated by H. pylori

“…H. pylori strain G27 is a clinical isolate which has been described previously [21]. G27/cag::kan is an isogenic derivative of H. pylori G27 in which a 1545 base pairs (bp) DNA fragment comprising part of the coding regions of hp0546 ( cagC ) and hp0547 ( cagA ) as well as the intergenic region between the two open reading frames (ORFs) has been replaced by a kanamycin resistance cassette via allelic exchange mutagenesis.…”

Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity

“…The protein toxin VacA produced by pathogenic Helicobacter pylori strains plays a major role in the pathogenesis of gastroduodenal diseases associated with infection by this bacterium (Blaser, 1993;Cover et al, 1993a;Marchetti et al, 1995;Xiang et al, 1995). Consistently, gastric epithelial erosion observed in these pathologies is mimicked in animal models by the oral administration of VacA (Telford et al, 1994).…”

H. pyloriselectively blocks EGFR endocytosis via the non-receptor kinase c-Abl and CagA

“…Helicobacter pylori can be grouped in two genetically distinct types, designated I and II. Type I strains harbouring the cag pathogenicity island (cagPAI) are generally associated with more severe disease as compared with type II strains (Xiang et al, 1995). The cagPAI encodes a type IV secretion system (TFSS) that translocates the bacterial effector protein CagA into host cells (Censini et al, 1996;Akopyants et al, 1998;Backert et al, 2000;Censini et al, 2001;Montecucco and Rappuoli, 2001).…”