title: CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Sicinschi
authors.forename: P
authors.initials: P
authors.lastname: Correa
authors.forename: R M
authors.initials: RM
authors.lastname: Peek
authors.forename: M C
authors.initials: MC
authors.lastname: Camargo
authors.forename: M B
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: J
authors.initials: J
authors.lastname: Romero-Gallo
authors.forename: S S
authors.initials: SS
authors.lastname: Hobbs
authors.forename: U
authors.initials: U
authors.lastname: Krishna
authors.forename: A
authors.initials: A
authors.lastname: Delgado
authors.forename: R
authors.initials: R
authors.lastname: Mera
authors.forename: L E
authors.initials: LE
authors.lastname: Bravo
authors.forename: B G
authors.initials: BG
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003105:Colombia; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori