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Gut. 1999 March; 44(3): 336–341.
PMCID: PMC1727424

Structure of cag pathogenicity island in Japanese Helicobacter pylori isolates

Abstract

BACKGROUNDcag pathogenicity island (PAI) is reported to be a major virulence factor of Helicobacter pylori.
AIM—To characterise cagA and the cag PAI in Japanese H pylori strains.
METHODSH pylori isolates from Japanese patients were evaluated for CagA by immunoblot, for cagA transcription by northern blot, and for cagA and 13 other cag PAI genes by Southern blot. cagA negative strains from Western countries were also studied. Induction of interleukin-8 secretion from gastric epithelial cells was also investigated.
RESULTS—All Japanese strains retained cagA. Fifty nine of 63 (94%) strains had all the cag PAI genes. In the remaining four, cag PAI was partially deleted, lacking cagA transcripts and not producing CagA protein. Details of the PAI of these strains were checked; three lacked cagB to cagQ (cagI) and continuously cagS to cag13 (cagII), and the remaining one lacked cagB to cag8. Western cagA negative strains completely lacked cag PAI including cagA. Nucleotide sequence analysis in one strain in which the cag PAI was partially deleted showed that the partial deletion contained 25 kb of cag PAI and the cagA promoter. Interleukin-8 induction was lower with the cag PAI partial deletion strains than with the intact ones. All Japanese cag PAI deleted strains were derived from patients with non-ulcer dyspepsia, whereas 41of 59 (70%) CagA-producing strains were from patients with peptic ulcers or gastric cancer (p<0.05).
CONCLUSIONS—Most Japanese H pylori strains had the intact cag PAI. However, some lacked most of the cag PAI in spite of the presence of cagA. Thus the presence of the cagA gene is not an invariable marker of cag PAI related virulence in Japanese strains.

Keywords: Helicobacter pylori; pathogenicity island; Japanese

Figure 1
Map of the cag pathogenicity island. The names of the genes are from GenBank accession number AC000108 and U60176. Cross bars indicate probes used in this study. Fifty nine of 63 strains isolated in Japan all had cagI and cagII. Large deletions were ...
Figure 2
Northern blot analysis of cagA transcripts from seven strains. cagA transcripts were present in T-57 (lane 2), T-1 (lane 5), and ATCC 43526 (lane 7), and absent from T-94 (lane 1), T-85, T-25 (lanes 3 and 4), and Tx30a (lane 6). The membrane was also ...
Figure 3
Junctional sequences of T-94, which has cag PAI deleted. cagII was present down to position 14 723 (GenBank accession number AC000108) in the middle of cag13. The cagA gene was present up to position 19 462 (GenBank accession number U60176). This position ...
Figure 4
Secretion of interleukin-8 (IL-8) from MKN-28 cells over the 16 hours after stimulation. T-77, T-78, T-79, T-81, T-82, T-90, T-100, T-102, T-103, T-108 strains were clinical isolates with an intact cag pathogenicity island (PAI). 43579 indicates ATCC ...

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