The alpha subunits of Francisella tularensis RNA polymerase

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DESCRIPTION (provided by applicant): Francisella tularensis, the aetiological agent of tularemia, is one of the most infectious bacterial pathogens currently known and a potential biological weapon. It is both an environmental organism and a pathogen, and must therefore survive under widely varying conditions. Strikingly, however, F. tularensis encodes relatively few transcription regulators. Inspection of the F. tularensis genome sequence reveals two genes, designated rpoA1 and rpoA2, encoding different a subunits of RNA polymerase (RNAP). This situation is without precedent; in all other bacterial genomes sequenced to date there is only one rpoA gene. Because a participates in promoter recognition through direct sequence-specific protein-DNA interactions, and because a is a common target for transcription activators, RNAP molecules that differ from one another with respect to their a content may have very different properties. Here we propose to take a combination of genetic and biochemical approaches to determine whether or not RNAP in F. tularensis contains two functionally distinct a subunits. These studies will have important implications for how gene expression is controlled in F. tularensis; the use of an RNAP population with different a subunits may represent a unique strategy for recognizing different classes of promoter and controlling transcription, one that might be exploited in the design of antimicrobials that specifically target F. tularensis.