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PMID: 8962108 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A

Abstract

cagA, 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 flanked 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.

MeSH Terms
Antigens, Bacterial/genetics Bacterial Proteins/genetics Base Sequence Chromosome Mapping Evolution, Molecular Genes, Bacterial Helicobacter pylori/genetics,pathogenicity Molecular Sequence Data Sequence Analysis Virulence/genetics
Chemicals
Antigens, Bacterial Bacterial Proteins cagA protein, Helicobacter pylori
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Censini S
Immunobiological Research Institute of Siena, Chiron Vaccines, Italy.
Lange C
Xiang Z
Crabtree J E
Ghiara P
Borodovsky M
Rappuoli R
Covacci A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1996-12-10
Pages
14648-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC26189
Subset
IM
Databases
GENBANK
A12521, A35146, D38778, J03986, L25845, L25848, M76598, P24421, P29721, P33566, S42614, U12817, U21963, U22457, U32720, U60176, U60177, X56727
SWISSPROT
D38778, J03986, L25845, L25848, P24421, P33566, S42614, U12817, U21963, U22457, U32720, X56727
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