cag , a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors

Abstract

ABSTRACTcagA, a gene that codes for an immunodominant antigen, is present only in Helicobacter pylori strains that are associated with severe forms of gastroduodenal disease (type I strains). We found that the genetic locus that contains cagA (cag) is part of a 40-kb DNA insertion that likely was acquired horizontally and integrated into the chromosomal glutamate racemase gene. This pathogenicity island is f lanked by direct repeats of 31 bp. In some strains, cag is split into a right segment (cagI) and a left segment (cagII) by a novel insertion sequence (IS605). In a minority of H. pylori strains, cagI and cagII are separated by an intervening chromosomal sequence. Nucleotide sequencing of the 23,508 base pairs that form the cagI region and the extreme 3 end of the cagII region reveals the presence of 19 ORFs that code for proteins predicted to be mostly membrane associated with one gene (cagE), which is similar to the toxin-secretion gene of Bordetella pertussis, ptlC, and the transport systems required for plasmid transfer, including the virB4 gene of Agrobacterium tumefaciens. Transposon inactivation of several of the cagI genes abolishes induction of IL-8 expression in gastric epithelial cell lines. Thus, we believe the cag region may encode a novel H. pylori secretion system for the export of virulence determinants.

Transcriptional analysis of the divergent cagAB genes encoded by the pathogenicity island of Helicobacter pylori

“…Surprisingly, no obvious ¹35 conserved regions (TTGACA) could be detected (Fig. 1 (Censini et al, 1996). d. The sequence of this oligonucleotide is complementary to the first 24 nucleotides of the coding sequence of the ␤-galactosidase gene from E. coli.…”

Prostaglandin E2 Prevents Helicobacter-Induced Gastric Preneoplasia and Facilitates Persistent Infection in a Mouse Model

“…22 In both cell types, COX-2 protein expression and PGE 2 secretion was induced by H. pylori in a dose-dependent manner, and independently of the Cag PAI ( Figure 1A-C). PGE 2 production was blocked in the presence of the COX inhibitor indomethacin ( Figure 1C), indicating that it is produced exclusively by COX enzymes in this setting.…”

“…7 Both cell types were grown in DMEM/Ham's F12 medium (1:1; Gibco) supplemented with 10% FCS and infected for 12 hours with H. pylori strains G27 or an isogenic mutant lacking the Cag pathogenicity island (PAI), G27 PAI. 22 Vaccination of mice was performed as stated in the supplemental methods.…”

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

“…The cagA gene is localized at one end of the cag pathogenicity island (cag PAI), a 40-kb DNA segment that is considered to be horizontally transferred into the H. pylori genome (Censini et al, 1996;Akopyants et al, 1998). Whereas almost all of the East Asian H. pylori isolates are cagA-positive, approximately half of the H. pylori strains isolated in Western countries do not carry cag PAI and thus are cagA negative.…”