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dc.contributor.advisor Seed, Patrick C en_US
dc.contributor.author Bateman, SL
dc.contributor.author Seed, PC
dc.coverage.spatial England
dc.date.accessioned 2012-01-10T15:58:49Z
dc.date.issued 2012-03
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/22221182
dc.identifier.citation Mol Microbiol, 2012, 83 (5), pp. 908 - 925
dc.identifier.uri http://hdl.handle.net/10161/4999
dc.description Dissertation en_US
dc.description.abstract 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 (RNIs), primarily through de-repression of hmpA, encoding a nitric oxide-detoxifying flavohaemoglobin. 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.
dc.format.extent 908 - 925
dc.language ENG
dc.relation.ispartof Mol Microbiol
dc.relation.isversionof 10.1111/j.1365-2958.2012.07977.x
dc.subject Animals
dc.subject Cell Line
dc.subject DNA, Bacterial
dc.subject Epigenesis, Genetic
dc.subject Escherichia coli
dc.subject Escherichia coli Proteins
dc.subject Fimbriae Proteins
dc.subject Gene Expression Regulation, Bacterial
dc.subject Macrophages
dc.subject Mice
dc.subject Promoter Regions, Genetic
dc.subject Reactive Nitrogen Species
dc.subject Sequence Deletion
dc.subject Sequence Inversion
dc.subject Virulence Factors
dc.title Epigenetic regulation of the nitrosative stress response and intracellular macrophage survival by extraintestinal pathogenic Escherichia coli.
dc.type Journal Article
dc.department Molecular Genetics and Microbiology en_US
duke.embargo.months 24 en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/22221182
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics/Pediatrics, Infectious Diseases
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Urology
pubs.publication-status Published
pubs.volume 83
dc.identifier.eissn 1365-2958

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