Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial survival by mitigating host immune responses.
An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the human gastric pathogen Helicobacter pylori was previously identified and characterized. In this study, we constructed H. pylori pgdA mutants in two mouse-adapted strains, X47 and B128, to investigate the role of PgdA in 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) when H. 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 an H. 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, the pgdA mutant showed a significantly attenuated ability to colonize mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With the cag PAI-positive strain B128, a significant colonization difference between the wild type and the pgdA mutant was observed at 3 weeks postinoculation (1.32 × 10(4) versus 1.85 × 10(3) CFU/gram of stomach). To monitor the immune responses elicited by H. pylori in the mouse infection model, we determined the concentrations of cytokines present in mouse sera. In the mice infected with the pgdA 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 the pgdA mutant-infected mice compared to the levels in the wild-type H. pylori-infected mice were also observed. These results indicated that H. pylori peptidoglycan deacetylation is an important mechanism for mitigating host immune detection; this likely contributes to pathogen persistence.
Wang
Ge
G
Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Maier
Susan E
SE
Lo
Leja F
LF
Maier
George
G
Dosi
Shruti
S
Maier
Robert J
RJ
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D018922:HL-60 Cells; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D009154:Mutation; D010457:Peptidoglycan / Q000378:metabolism*; D013270:Stomach / Q000276:immunology / Q000382:microbiology
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D010457:Peptidoglycan; D000581:Amidohydrolases
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