Isogenic mutants of the cag pathogenicity island of Helicobacter pylori in the mouse model of infection: effects on colonization efficiency.
Strains of Helicobacter pylori that contain the cag pathogenicity island (cag PAI) are associated with increased virulence and severe clinical outcomes. To evaluate the role of the cag island in infection, isogenic null mutations were generated in two clinical isolates (SS1 and Iris1) with distinct genetic backgrounds. When tested for their ability to establish infection in the stomach of CD1/SPF mice, at the early phase of infection, strains in which cagE, ORF528, ORF527 or ORF525 were inactivated showed a reduced capacity to initiate colonization compared to the wild-type strain. Strains with a mutation in the ORF524 gene were more efficient than the other mutants, but still less efficient than the wild-type strain. Mutation in the effector protein, CagA, which is injected into host cells and tyrosine-phosphorylated, did not change the colonization efficiency. In conclusion, all cag genes analysed, with the exception of the effector protein, CagA, influenced the early phase of colonization in the mouse model of infection. These results suggest that the structure of the H. pylori secretion apparatus itself is involved in this process.
Marchetti
Marta
M
Immunobiological Research Institute of Siena (IRIS) Chiron Spa, Via Fiorentina 1, 53100 Siena, Italy. mmarchet@pasteur.fr
Rappuoli
Rino
R
D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori