The Brucella abortus Cu,Zn superoxide dismutase is required for optimal resistance to oxidative killing by murine macrophages and wild-type virulence in experimentally infected mice
| Autor: | Jason M. Gee, R. Martin Roop, Wai-Leung Ng, Michael E. Kovach, Gregory T. Robertson, Michelle Wright Valderas, John M. Richardson, Vanessa K. Grippe, Malcolm E. Winkler |
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| Rok vydání: | 2005 |
| Předmět: |
Immunology
Mutant Virulence Brucella abortus Host Factor 1 Protein Microbiology Brucellosis Superoxide dismutase chemistry.chemical_compound Mice Animals Humans Cells Cultured Host factor Respiratory Burst NADPH oxidase biology Superoxide Dismutase Wild type Gene Expression Regulation Bacterial Molecular Pathogenesis Respiratory burst Mice Inbred C57BL Infectious Diseases chemistry Apocynin Mutation biology.protein Macrophages Peritoneal Parasitology Female |
| Zdroj: | Infection and immunity. 73(5) |
| ISSN: | 0019-9567 |
| Popis: | Two-dimensional gel electrophoretic analysis of cell lysates fromBrucella abortus2308 and the isogenichfqmutant Hfq3 revealed that the RNA binding protein Hfq (also known as host factor I or HF-I) is required for the optimal stationary phase production of the periplasmic Cu,Zn superoxide dismutase SodC. An isogenicsodCmutant, designated MEK2, was constructed fromB. abortus2308 by gene replacement, and thesodCmutant exhibited much greater susceptibility to killing by O2−generated by pyrogallol and the xanthine oxidase reaction than the parental 2308 strain supporting a role for SodC in protecting this bacterium from O2−of exogenous origin. TheB. abortus sodCmutant was also found to be much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and the attenuation displayed by MEK2 in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon (IFN-γ). The attenuation displayed by theB. abortus sodCmutant in both resting and IFN-γ-activated macrophages was alleviated, however, when these host cells were treated with the NADPH oxidase inhibitor apocynin. Consistent with its increased susceptibility to killing by cultured murine macrophages, theB. abortus sodCmutant also displayed significant attenuation in experimentally infected C57BL6J mice compared to the parental strain. These experimental findings indicate that SodC protectsB. abortus2308 from the respiratory burst of host macrophages. They also suggest that reduced SodC levels may contribute to the attenuation displayed by theB. abortus hfqmutant Hfq3 in the mouse model. |
| Databáze: | OpenAIRE |
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