Journal
CLINICAL MICROBIOLOGY AND INFECTION
Volume 16, Issue 4, Pages 369-378Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1469-0691.2009.02811.x
Keywords
CagA; cagA 3'region; CagA multimerization motif; EPIYA; ESS; H; pylori; WSS
Categories
Funding
- NATIONAL CANCER INSTITUTE [R01CA077955, P50CA095103, P01CA028842, R29CA077955] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK058404, R01DK073902, R01DK058587] Funding Source: NIH RePORTER
- NCI NIH HHS [P01 CA028842-24, R01 CA077955-11, P50 CA095103-07, P50 CA095103-08, P01 CA 28842, P50 CA95103, P50 CA095103, R01 CA077955, P01 CA028842, R29 CA077955, R01 CA 77955, P01 CA028842-23, R01 CA077955-12] Funding Source: Medline
- NIDDK NIH HHS [R01 DK058587-08, P30 DK058404, R01 DK058587-07, R01 DK073902-03, R01 DK 73902, P30 DK058404-07, R01 DK 58587, P30DK058404, R01 DK073902-04, P30 DK058404-08, R01 DK058587, R01 DK073902] Funding Source: Medline
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P>The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3' region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p < 0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.
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