Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease.
Helicobacter pylori infection is associated with a variety of outcomes ranging from seemingly asymptomatic coexistence to peptic ulcer disease and gastric cancer. The cag pathogenicity island (PAI) contains genes associated with a more aggressive phenotype and has been suggested to be a determinant of severe disease outcome. The cagA gene has served as a marker for the cag PAI. However, the presence of this single gene does not necessarily indicate the presence of a complete set of cag PAI genes. We have analyzed the composition of the cag PAI in 66 clinical isolates obtained from patients with duodenal ulcer, gastric cancer, and nonulcer dyspepsia. Hybridization of DNA to microarrays containing all the genes of the cag PAI showed that 76 and 9% of the strains contained all or none of the cag PAI genes, respectively. Partial deletions of the cag PAI were found in 10 isolates (15%), of which 3 were cagA negative. The ability to induce interleukin-8 (IL-8) production in AGS cells was correlated to the presence of a complete cag PAI. Strains carrying only parts of the island induced IL-8 at levels significantly lower than those induced by cag PAI-positive isolates. The presence of an intact cag PAI correlates with development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease (odds ratio, 5.13; 95% confidence interval, 1.5 to 17.4). Partial deletions of the cag PAI appear to be sufficient to render the organism less pathogenic.
Swedish Institute for Infectious Disease Control, Solna, Sweden.
Christina
C
Nilsson
Anna
A
Sillén
Lena
L
Eriksson
Mona-Lisa
ML
Strand
Helena
H
Enroth
Staffan
S
Normark
Per
P
Falk
Lars
L
Engstrand
D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001483:Base Sequence; D004381:Duodenal Ulcer / Q000382:microbiology*; D004415:Dyspepsia / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000382:microbiology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori