Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion.
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.
Argent
Richard H
RH
Division of Pre-Clinical Oncology, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.|Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.|Wolfson Digestive Diseases Centre, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Hale
James L
JL
Wolfson Digestive Diseases Centre, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.|Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
El-Omar
Emad M
EM
Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Atherton
John C
JC
Wolfson Digestive Diseases Centre, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.|Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
D020816:Amino Acid Motifs; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001211:Asia, Western; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005202:Asia, Eastern; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine