Small Molecule Control of Virulence Gene Expression in Francisella tularensis

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Small Molecule Control of Virulence Gene Expression in Francisella tularensis

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Title: Small Molecule Control of Virulence Gene Expression in Francisella tularensis
Author: Charity, James Carl; Blalock, LeeAnn T.; Costante-Hamm, Michelle M.; Kasper, Dennis Lee; Dove, Simon L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Charity, 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.
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Abstract: In 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.
Published Version: doi://10.1371/journal.ppat.1000641
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763202/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10021579

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