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Publication Abstract from PubMed

The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with the sigma(70)-associated RNAP holoenzyme (RNAPsigma(70)), forming a virulence-specialized polymerase. These factors activate Francisella pathogenicity island (FPI) gene expression, which is required for virulence, but the mechanism is unknown. Here we report FtRNAPsigma(70)-promoter-DNA, FtRNAPsigma(70)-(MglA-SspA)-promoter DNA, and FtRNAPsigma(70)-(MglA-SspA)-ppGpp-PigR-promoter DNA cryo-EM structures. Structural and genetic analyses show MglA-SspA facilitates sigma(70) binding to DNA to regulate virulence and virulence-enhancing genes. Our Escherichia coli RNAPsigma(70-)homodimeric EcSspA structure suggests this is a general SspA-transcription regulation mechanism. Strikingly, our FtRNAPsigma(70)-(MglA-SspA)-ppGpp-PigR-DNA structure reveals ppGpp binding to MglA-SspA tethers PigR to promoters. PigR in turn recruits FtRNAP alphaCTDs to DNA UP elements. Thus, these studies unveil a unique mechanism for Ft pathogenesis involving a virulence-specialized RNAP that employs two (MglA-SspA)-based strategies to activate virulence genes.

Structural Basis for Virulence Activation of Francisella tularensis.,Travis BA, Ramsey KM, Prezioso SM, Tallo T, Wandzilak JM, Hsu A, Borgnia M, Bartesaghi A, Dove SL, Brennan RG, Schumacher MA Mol Cell. 2021 Jan 7;81(1):139-152.e10. doi: 10.1016/j.molcel.2020.10.035. Epub , 2020 Nov 19. PMID:33217319^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.