Open AccessPeptidoglycan Deacetylation in Helicobacter pylori Contributes to Bacterial Survival by Mitigating Host Immune Responses
Author(s) -
Ge Wang,
Susan E. Maier,
Leja F. Lo,
George Maier,
Shruti Dosi,
Robert J. Maier
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00307-10
Subject(s) - biology , peptidoglycan , microbiology and biotechnology , immune system , helicobacter pylori , mutant , pathogen , lysozyme , in vivo , wild type , immunology , bacteria , gene , biochemistry , genetics
An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the human gastric pathogenHelicobacter pylori was previously identified and characterized. In this study, we constructedH. pylori pgdA mutants in two mouse-adapted strains, X47 and B128, to investigate the role of PgdAin vivo (to determine the mutants’ abilities to colonize mice and to induce an immune response).H. pylori pgdA mutant cells showed increased sensitivity to lysozyme compared to the sensitivities of the parent strains. We demonstrated that the expression of PgdA was significantly induced (3.5-fold) whenH. pylori cells were in contact with macrophages, similar to the effect observed with oxidative stress as the environmental inducer. Using a mouse infection model, we first examined the mouse colonization ability of anH. pylori pgdA mutant in X47, a strain deficient in the major pathway (cag pathogenicity island [PAI] encoded) for delivery of peptidoglycan into host cells. No animal colonization difference between the wild type and the mutant was observed 3 weeks after inoculation. However, thepgdA mutant showed a significantly attenuated ability to colonize mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With thecag PAI-positive strain B128, a significant colonization difference between the wild type and thepgdA mutant was observed at 3 weeks postinoculation (1.32 × 104 versus 1.85 × 103 CFU/gram of stomach). To monitor the immune responses elicited byH. pylori in the mouse infection model, we determined the concentrations of cytokines present in mouse sera. In the mice infected with thepgdA mutant strain, we observed a highly significant increase in the level of MIP-2. In addition, significant increases in interleukin-10 and tumor necrosis factor alpha in thepgdA mutant-infected mice compared to the levels in the wild-typeH. pylori -infected mice were also observed. These results indicated thatH. pylori peptidoglycan deacetylation is an important mechanism for mitigating host immune detection; this likely contributes to pathogen persistence.