Investigation of the biological relevance of Helicobacter pylori cagE locus diversity, presence of CagA tyrosine phosphorylation motifs and vacuolating cytotoxin genotype on IL-8 induction in gastric epithelial cells.
Isolates of Helicobacter pylori from dyspeptic patients in England and South Africa were tested for ability to induce interleukin-8 (IL-8) in gastric cells. All isolates were cagA-positive, which was used as a marker for the presence of the cag pathogenicity island. The aims were to determine if activities were related to diversity within cagE (HP0544), a locus encoding a key component in the Type IV secretion system, and if disease severity might be linked to a combination of strain features. We found that isolates were heterogeneous in ability to induce IL-8 activity with the 23 positive isolates (59%) showing activities ranging from 260 to 3200 pg ml(-1). The cagE locus was detected in most isolates and RFLP analysis of a 1.52-kb internal fragment showed interstrain diversity with 12 combined (MboI/NlaIII) types. Most cagE genotypes were not associated with IL-8 induction, however two genotypes were found only in IL-8-inducing strains and one genotype was associated with lack of IL-8 induction. IL-8 activity was not associated with either the number or composition of cagA tyrosine phosphorylation motifs and vacA m-type. Although we found a weak association between cagE type and the ability to induce IL-8, our results imply that gastric cell factors or bacterial factors other than vacA, cagA and cagE are involved in the induction of IL-8 and the development of severe gastric disease.
Owen
Robert J
RJ
Laboratory of Enteric Pathogens, Central Public Health Laboratory, 61 Colindale Avenue, London NW9 5HT, UK. rowen@phls.nhs.uk
Sharp
Sally
S
Lawson
Andrew J
AJ
Durrani
Zarmina
Z
Rijpkema
Sjoerd
S
Kidd
Mark
M
D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004415:Dyspepsia / Q000382:microbiology / Q000503:physiopathology; D004847:Epithelial Cells / Q000382:microbiology; D005753:Gastric Mucosa / Q000382:microbiology; D005767:Gastrointestinal Diseases / Q000382:microbiology / Q000503:physiopathology; D014644:Genetic Variation; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D010766:Phosphorylation; D012720:Severity of Illness Index; D014443:Tyrosine / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C103937:PicB protein, Helicobacter pylori; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine