Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer.

Abstract

Helicobacter pylori has been associated with gastritis, peptic ulcer, and gastric adenocarcinoma. We report the nucleotide sequence and expression of an immunodominant antigen of H. pylori and the immune response to the antigen during disease. The antigen, named CagA (cytotoxin-associated gene A), is a hydrophilic, surface-exposed protein of 128 kDa produced by most clinical isolates. The size of the cagA gene and its protein varies in different strains by a mechanism that involves duplication of regions within the gene. Clinical isolates that do not produce the antigen do not have the gene and are unable to produce an active vacuolating cytotoxin. An ELISA to detect the immune response against a recombinant fragment of this protein detects 75.3% of patients with gastroduodenal diseass and 100% of patients with duodenal ulcer (P < 0.0005), suggesting that only bacteria harboring this protein are associated with disease.

Analyses of the cag pathogenicity island of Helicobacter pylori

“…Comparison of sequences from the cloned fragments with those from cosmid 36 identified the point of divergence between cag ¹ and cag þ strains at the left end of the cag region. Just after this point of divergence, the ᮊ 1998 Blackwell Science Ltd, Molecular Microbiology, 28, 37-53 sequences from the cag ¹ strains matched a sequence previously reported by Covacci et al (1993) that is 1.1 kb to the right of the cagA gene (Fig. 5B).…”

“…Much remains to be learned about the role of the cag PAI in colonization, persistence and disease; the evolutionary forces that determine the differences in prevalence of the cag PAI among H. pylori isolates from different human populations (compare, for example, Pan et al, 1997and Shimoyama et al, 1997and Covacci et al, 1993; the interspecies and perhaps interkingdom DNA transfer events that have all contributed to this PAI, with its complement of homologies to motifs of both eukaryotic and prokaryotic proteins; and how the presence/absence of the cag PAI may have affected selection for other polymorphic H. pylori traits such as toxigenicity or Lewis B adherence.…”

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

“…CagA is a 120B145-kDa H. pylori protein that is encoded by the cagA gene (Covacci et al, 1993;Tummuru et al, 1993). 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).…”

Assessment of the mosaic structure in the Helicobacter pylori cagA gene 3′-region using an improved polymerase chain reaction–based assay

“…DNA sequence analysis of the cagA gene has revealed the presence of a conserved 5'-region and a highly variable 3'-region [1][2][3]. Previous studies have shown that the CagA cytotoxin is directly injected into epithelial cells via a type IV secretion system, encoded by genes located in the cag -pathogenicity island (cag-PAI) [1,4,5].…”

“…DNA sequence analysis of the cagA gene has revealed the presence of a conserved 5'-region and a highly variable 3'-region [1][2][3]. Previous studies have shown that the CagA cytotoxin is directly injected into epithelial cells via a type IV secretion system, encoded by genes located in the cag -pathogenicity island (cag-PAI) [1,4,5]. In the host cell, CagA localises to the inner surface of the plasma membrane and undergoes phosphorylation on specific tyrosine residues within repeating penta amino acid Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs, and in some cases Glu-Pro-Ile-Tyr-Thr (EPIYT), present at the C-terminus of the protein [2,6,7].…”