Structural Basis for Virulence Activation of Francisella tularensis.
Journal Article (Journal Article)
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 σ70-associated RNAP holoenzyme (RNAPσ70), 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 FtRNAPσ70-promoter-DNA, FtRNAPσ70-(MglA-SspA)-promoter DNA, and FtRNAPσ70-(MglA-SspA)-ppGpp-PigR-promoter DNA cryo-EM structures. Structural and genetic analyses show MglA-SspA facilitates σ70 binding to DNA to regulate virulence and virulence-enhancing genes. Our Escherichia coli RNAPσ70-homodimeric EcSspA structure suggests this is a general SspA-transcription regulation mechanism. Strikingly, our FtRNAPσ70-(MglA-SspA)-ppGpp-PigR-DNA structure reveals ppGpp binding to MglA-SspA tethers PigR to promoters. PigR in turn recruits FtRNAP αCTDs 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.
Full Text
Duke Authors
Cited Authors
- Travis, BA; Ramsey, KM; Prezioso, SM; Tallo, T; Wandzilak, JM; Hsu, A; Borgnia, M; Bartesaghi, A; Dove, SL; Brennan, RG; Schumacher, MA
Published Date
- January 7, 2021
Published In
Volume / Issue
- 81 / 1
Start / End Page
- 139 - 152.e10
PubMed ID
- 33217319
Pubmed Central ID
- PMC7959165
Electronic International Standard Serial Number (EISSN)
- 1097-4164
Digital Object Identifier (DOI)
- 10.1016/j.molcel.2020.10.035
Language
- eng
Conference Location
- United States