| Epigenetic Regulation of the Nitrosative Stress Response and Intracellular Macrophage Survival by Extraintestinal Pathogenic Escherichia coli. | |
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MedLine Citation:
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PMID: 22221182 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection, and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor IHF. In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNI), primarily through de-repression of hmpA, encoding a nitric oxide detoxifying flavohemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX. |
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Authors:
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Stacey L Bateman; Patrick C Seed |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-5 |
Journal Detail:
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Title: Molecular microbiology Volume: - ISSN: 1365-2958 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712028 Medline TA: Mol Microbiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Blackwell Publishing Ltd. |
Affiliation:
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Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710 Center for Microbial Pathogenesis, Duke University School of Medicine, Durham, NC 27710. Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710. |
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