Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype

Rahul A. Aras, Yongchan Lee, Sung Kook Kim, Dawn Israel, Richard M. Peek, Martin J. Blaser

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


The highly diverse bacterium Helicobacter pylori, which persistently colonizes the human stomach, provides models to study the role of genome plasticity in host adaptation. Within H. pylori populations from 2 colonized individuals, intragenomic recombination between cagA DNA repeat sequences leads to deletion or duplication of tyrosine phosphorylation sites in the CagA protein, which is injected by a type IV secretion system into host cells. Experimental coculture of gastric epithelial cells with the strains containing these naturally occurring CagA phosphorylation site variants induced markedly divergent host cell morphologic responses. Mutants were constructed in which a phosphorylation site was either added or deleted in the expressed CagA protein; coculture studies confirmed that the naturally occurring differences in CagA phosphorylation are responsible for the observed phenotypic variation. These findings indicate that within an individual host, intragenomic recombination between H. pylori repetitive DNA produces strain variants differing in their signals to host cells.

Original languageEnglish
Pages (from-to)486-496
Number of pages11
JournalJournal of Infectious Diseases
Issue number4
Publication statusPublished - 2003 Aug 15

Bibliographical note

Funding Information:
Received 26 September 2002; accepted 21 March 2003; electronically published 31 July 2003. Financial support: National Institutes of Health (grants R01 GM63270, R01 DK58587, and 5T32 AI07180-21, and the National Cancer Institute Cancer Core); Medical Research Service of the Department of Veterans Affairs. a R.A.A. and Y.L. contributed equally to this work. Reprints or correspondence: Dr. Yongchan Lee, Dept. of Internal Medicine, Div. of Gastroenterology, Yonsei University College of Medicine, Seodaemunku Shinchondong 134, Seoul, Korea 120-752 (

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases


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