BACKGROUND AND AIMS: The roles of the virD4 and the cagG genes in the cag pathogenicity island of Helicobacter pylori for gastroduodenal pathogenesis are unclear and their roles in vivo have not been examined. METHODS: Seven week old male Mongolian gerbils were inoculated with the wild type H pylori TN2GF4, its isogenic virD4, or cagG mutants. Animals were sacrificed at 4, 12, and 24 weeks after inoculation. Gastric inflammation and H pylori density were evaluated by histology, inflammatory response (as measured by interleukin (IL)-1beta mRNA levels), proliferative activity (as assessed by 5'-bromo-2'deoxyuridine labelling indices), and host systemic reaction (as measured by anti-H pylori IgG antibody). RESULTS: Degree of gastric inflammation, proliferative activity, and mucosal IL-1beta mRNA levels remained low throughout the first 12 weeks in gerbils infected with the virD4 mutants. Degree of gastric inflammation and proliferative activity increased at 24 weeks with the virD4 mutants reaching levels comparative with those seen at four weeks with the wild-type strains. Mucosal IL-1beta mRNA levels were also increased at 24 weeks with the virD4 mutants and levels at 24 weeks were similar between the wild-type and virD4 mutants. In contrast, gerbils infected with the cagG mutants had reduced ability to colonise gerbils, and no or little gastric inflammation or proliferative activity was observed. CONCLUSIONS: Loss of the virD4 gene temporally retarded but did not abrogate gastric inflammation. Loss of the cagG gene abolished gastric inflammation partially via reduced ability to colonise gerbils. Unknown factors related to the type IV secretion system other than CagA may influence gastric inflammation.
BACKGROUND AND AIMS: The roles of the virD4 and the cagG genes in the cag pathogenicity island of Helicobacter pylori for gastroduodenal pathogenesis are unclear and their roles in vivo have not been examined. METHODS: Seven week old male Mongolian gerbils were inoculated with the wild type H pylori TN2GF4, its isogenic virD4, or cagG mutants. Animals were sacrificed at 4, 12, and 24 weeks after inoculation. Gastric inflammation and H pylori density were evaluated by histology, inflammatory response (as measured by interleukin (IL)-1beta mRNA levels), proliferative activity (as assessed by 5'-bromo-2'deoxyuridine labelling indices), and host systemic reaction (as measured by anti-H pylori IgG antibody). RESULTS: Degree of gastric inflammation, proliferative activity, and mucosal IL-1beta mRNA levels remained low throughout the first 12 weeks in gerbils infected with the virD4 mutants. Degree of gastric inflammation and proliferative activity increased at 24 weeks with the virD4 mutants reaching levels comparative with those seen at four weeks with the wild-type strains. Mucosal IL-1beta mRNA levels were also increased at 24 weeks with the virD4 mutants and levels at 24 weeks were similar between the wild-type and virD4 mutants. In contrast, gerbils infected with the cagG mutants had reduced ability to colonise gerbils, and no or little gastric inflammation or proliferative activity was observed. CONCLUSIONS: Loss of the virD4 gene temporally retarded but did not abrogate gastric inflammation. Loss of the cagG gene abolished gastric inflammation partially via reduced ability to colonise gerbils. Unknown factors related to the type IV secretion system other than CagA may influence gastric inflammation.
Authors: J F Tomb; O White; A R Kerlavage; R A Clayton; G G Sutton; R D Fleischmann; K A Ketchum; H P Klenk; S Gill; B A Dougherty; K Nelson; J Quackenbush; L Zhou; E F Kirkness; S Peterson; B Loftus; D Richardson; R Dodson; H G Khalak; A Glodek; K McKenney; L M Fitzegerald; N Lee; M D Adams; E K Hickey; D E Berg; J D Gocayne; T R Utterback; J D Peterson; J M Kelley; M D Cotton; J M Weidman; C Fujii; C Bowman; L Watthey; E Wallin; W S Hayes; M Borodovsky; P D Karp; H O Smith; C M Fraser; J C Venter Journal: Nature Date: 1997-08-07 Impact factor: 49.962
Authors: S Censini; C Lange; Z Xiang; J E Crabtree; P Ghiara; M Borodovsky; R Rappuoli; A Covacci Journal: Proc Natl Acad Sci U S A Date: 1996-12-10 Impact factor: 11.205
Authors: Y Sawada; Y Kuroda; H Sashio; N Yamamoto; Y Tonokatsu; T Sakagami; Y Fukuda; T Shimoyama; T Nishigami; K Uematsu Journal: J Gastroenterol Date: 1998 Impact factor: 7.527
Authors: M J Blaser; G I Perez-Perez; H Kleanthous; T L Cover; R M Peek; P H Chyou; G N Stemmermann; A Nomura Journal: Cancer Res Date: 1995-05-15 Impact factor: 12.701
Authors: L T Nguyen; T Uchida; Y Tsukamoto; T D Trinh; L Ta; H B Mai; H S Le; D Q D Ho; H H Hoang; T Matsuhisa; T Okimoto; M Kodama; K Murakami; T Fujioka; Y Yamaoka; M Moriyama Journal: Eur J Clin Microbiol Infect Dis Date: 2010-04-07 Impact factor: 3.267
Authors: Takahiko Kudo; Hong Lu; Jeng-Yih Wu; Tomoyuki Ohno; Michael J Wu; Robert M Genta; David Y Graham; Yoshio Yamaoka Journal: Gastroenterology Date: 2007-01-05 Impact factor: 22.682
Authors: Richard L Ferrero; Patrick Avé; Delphine Ndiaye; Jean-Christophe Bambou; Michel R Huerre; Dana J Philpott; Sylvie Mémet Journal: Infect Immun Date: 2007-12-10 Impact factor: 3.441
Authors: Débora Menezes da Costa; Eliane dos Santos Pereira; Silvia Helena Barem Rabenhorst Journal: World J Gastroenterol Date: 2015-10-07 Impact factor: 5.742
Authors: Aung Soe Lin; Mark S McClain; Amber C Beckett; Rhonda R Caston; M Lorena Harvey; Beverly R E A Dixon; Anne M Campbell; Jennifer H B Shuman; Neha Sawhney; Alberto G Delgado; John T Loh; M Blanca Piazuelo; Holly M Scott Algood; Timothy L Cover Journal: mBio Date: 2020-06-30 Impact factor: 7.867