TITLE

EVOLUTION OF THE HELICOBACTER PYLORI VACA TOXIN BY RECOMBINATION IN VIVO

AUTHOR(S)
Aviles, F.; Letley, D.P.; Gonzalez, G.; Torres, J.; Atherton, J.C.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA17
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: The H pylori vacuolating cytotoxin, VacA, varies between strains as a result of genetic recombination. The three main types have different toxicity (s1/m1>s1/m2>s2/m2) and this results in different disease associations. We aimed to show whether VacA can evolve to alter its toxicity within an individual stomach. Methods: Single H pylori colonies were cultured From gastric biopsies from a Mexican patient with duodenal ulcer and typed for the toxin gene, vacA, by allele specific PCR. The relationship between isolates was determined by two PCR based genomic fingerprinting methods, random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP), and for two isolates of different vacA type by partial sequencing of the housekeeping genes, A/G adenine glycosylase (mutY) and GTPase (yphC). For these two isolates, vacA was sequenced and vacuolating activity was determined on the gastric cell line, AGS. Results: Among 11 individual isolates cultured, we found 4 of vacA type sl/ml and 7 of type s1/m2. RAPD and AFLP analysis showed that all isolates were closely related. Nucleotide sequencing of mutY and yphC confirmed a clonal origin. The vacA sequence of candidate vacA s1/m1 and s1/m2 clones showed differences in two vacA segments of 439 and 378 base pairs, respectively. Outside these regions, vacA nucleotide sequences were identical. The vacA s1/m1 clone induced AGS cell vacuolation whereas the s1/m2 clone induced no vacuolation. Conclusion/Discussion: We have demonstrated evolution, by homologous recombination, of the toxin gene, vacA, and hence of toxin phenotype within an individual stomach. From our vacA sequence data, it appears most likely that the less pathogenic strain is the result of this evolution process. Evolution of VacA in vivo might represents an adaptation process For survival in the changing gastric environment. Changing H pylori virulence within an individual stomach has important implications for pathogenicity...
ACCESSION #
9747372

 

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