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J Med Microbiol 57 (2008), 1062-1067; DOI: 10.1099/jmm.0.2008/001818-0
© 2008 Society for General Microbiology
ISSN 1473-5644

Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion

Richard H. Argent1,2,3,{dagger}, James L. Hale1,2,{dagger}, Emad M. El-Omar4 and John C. Atherton1,2

1 Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK

2 Wolfson Digestive Diseases Centre, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK

3 Division of Pre-Clinical Oncology, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK

4 Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

Correspondence
Richard H. Argent
richard.argent{at}nottingham.ac.uk

Received 10 March 2008
Accepted 30 May 2008

Helicobacter pylori strains from East Asia have an ‘East Asian’ type of CagA that is more active and predominantly comprises a single type. Strains from other countries have a ‘western’ type of CagA, which is less active and comprises many different types generated by intragenomic recombination. Co-culture of AGS gastric epithelial cells with isolates of western strains that displayed microevolution in CagA showed that isolates with additional copies of the C motif induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells with western and East Asian strains, each expressing CagA with a single copy of the C or D motif, showed that East Asian strains induced significantly more IL-8 secretion. Analysis of the different CagA types from data deposited in GenBank and from the literature showed that western CagA is significantly more likely to undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is of the corresponding D motif. Taken together, the data suggest that the already highly active East Asian CagA with one D motif has no requirement to increase its virulence, whereas the less active western CagA displays flexibility in its capacity to increase its number of tyrosine phosphorylation motifs to become more virulent.

Abbreviations: cag PAI, cytotoxin-associated gene pathogenicity island; CI, confidence interval; Csk, C-terminal Src kinase; IL-8, interleukin-8; OR, odds ratio; RAPD-PCR, random amplified polymorphic DNA PCR; TPM, tyrosine phosphorylation motif; VR, cagA 3' variable region.

{dagger}These authors contributed equally to this work.




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