| DksA-dependent resistance of Salmonella enterica Serovar Typhimurium against the Antimicrobial Activity of Inducible Nitric Oxide Synthase. | |
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MedLine Citation:
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PMID: 22311927 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In coordination with the ppGpp alarmone, the RNA polymerase regulatory protein DksA controls the stringent response of eubacteria, negatively regulating transcription of translational machinery and directly activating amino acid promoters and de novo amino acid biosynthesis. Given the effects of nitric oxide (NO) on amino acid biosynthetic pathways and the intimate relationship of DksA with amino acid synthesis and transport, we tested whether DksA contributes to the resistance of Salmonella to reactive nitrogen species (RNS). Our studies show that the zinc finger predicted to position DksA in the secondary channel of the RNA polymerase is essential for the resistance of S. Typhimurium to RNS in a murine model of systemic salmonellosis. Despite exhibiting auxotrophies for various amino acids, ΔdksA mutant Salmonella regain virulence in mice lacking inducible NO synthase (iNOS). DksA is also important for growth of this intracellular pathogen in the presence of NO congeners generated by iNOS during the innate response of murine macrophages. Accordingly, dksA-mutant Salmonella are hypersusceptible to chemically generated NO, a phenotype that can be prevented by adding amino acids. The DksA-dependent antinitrosative defenses do not rely on the Hmp flavohemoprotein that detoxifies NO to NO(3)(-), and appear to operate independently of the ppGpp alarmone. Our investigations are consistent with a model by which NO produced in the innate response to Salmonella exerts considerable pressure on amino acid biosynthesis. The cytotoxicity of NO against Salmonella amino acid biosynthetic pathways is antagonized in great part by the DksA-dependent regulation of amino acid biosynthesis and transport. |
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Authors:
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Calvin A Henard; Andrés Vázquez-Torres |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-6 |
Journal Detail:
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Title: Infection and immunity Volume: - ISSN: 1098-5522 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology, University of Colorado School of Medicine, Mail Box 8333; Room P18-9131, Aurora, CO 80045. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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