HELICOBACTER

Roles of virD4 and cagG genes in the cag pathogenicity island of Helicobacter pylori using a Mongolian gerbil model

H Saito¹, Y Yamaoka², S Ishizone¹, F Maruta¹, A Sugiyama¹, D Y Graham², K Yamauchi³, H Ota⁴, S Miyagawa¹

¹ Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
² Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
³ Department of Laboratory Medicine, School of Health Science, Shinshu University Hospital, Matsumoto, Nagano, Japan
⁴ Department of Biomedical Laboratory Sciences, School of Health Science, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

Correspondence to:
Correspondence to:
Dr Y Yamaoka
Michael E DeBakey Veterans Affairs Medical Center (111D), Rm 3A-320, 200 Holcombe Blvd, Houston, TX 77030, USA; yyamaoka{at}bcm.tmc.edu

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)-1ß 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-1ß 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-1ß 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.

Abbreviations: AI, arbitrary index; BrdU, 5'-bromo-2'deoxyuridine; CFU, colony forming units; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IL, interleukin; MNC, mononuclear cells; PAI, pathogenicity island; PCR, polymerase chain reaction; PMN, polymorphonuclear cells, RT, reverse transcription; vir, virulent

Keywords: Helicobacter pylori; cag pathogenicity island; cagG; virD4; Mongolian gerbils

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