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dc.contributor.authorCharity, James Carl
dc.contributor.authorBlalock, LeeAnn T.
dc.contributor.authorCostante-Hamm, Michelle M.
dc.contributor.authorKasper, Dennis Lee
dc.contributor.authorDove, Simon L.
dc.date.accessioned2012-12-10T21:10:08Z
dc.date.issued2009
dc.identifier.citationCharity, James C., LeeAnn T. Blalock, Michelle M. Costante-Hamm, Dennis L. Kasper, and Simon L. Dove. 2009. Small molecule control of virulence gene expression in Francisella tularensis. PLoS Pathogens 5(10): e1000641.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10021579
dc.description.abstractIn Francisella tularensis, the SspA protein family members MglA and SspA form a complex that associates with RNA polymerase (RNAP) to positively control the expression of virulence genes critical for the intramacrophage growth and survival of the organism. Although the association of the MglA-SspA complex with RNAP is evidently central to its role in controlling gene expression, the molecular details of how MglA and SspA exert their effects are not known. Here we show that in the live vaccine strain of F. tularensis (LVS), the MglA-SspA complex works in concert with a putative DNA-binding protein we have called PigR, together with the alarmone guanosine tetraphosphate (ppGpp), to regulate the expression of target genes. In particular, we present evidence that MglA, SspA, PigR and ppGpp regulate expression of the same set of genes, and show that mglA, sspA, pigR and ppGpp null mutants exhibit similar intramacrophage growth defects and are strongly attenuated for virulence in mice. We show further that PigR interacts directly with the MglA-SspA complex, suggesting that the central role of the MglA and SspA proteins in the control of virulence gene expression is to serve as a target for a transcription activator. Finally, we present evidence that ppGpp exerts its effects by promoting the interaction between PigR and the RNAP-associated MglA-SspA complex. Through its responsiveness to ppGpp, the contact between PigR and the MglA-SspA complex allows the integration of nutritional cues into the regulatory network governing virulence gene expression.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.ppat.1000641en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763202/pdf/en_US
dash.licenseLAA
dc.subjectinfectious diseasesen_US
dc.subjectbacterial infectionsen_US
dc.subjectmicrobiologyen_US
dc.subjectcellular microbiologyen_US
dc.subjectpathogenesisen_US
dc.titleSmall Molecule Control of Virulence Gene Expression in Francisella tularensisen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorCharity, James Carl
dc.date.available2012-12-10T21:10:08Z
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1371/journal.ppat.1000641*
dash.contributor.affiliatedCharity, James Carl
dash.contributor.affiliatedDove, Simon
dash.contributor.affiliatedKasper, Dennis


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