Impacts of Borrelia burgdorferi Gac protein on infectivity and regulation of virulence protein expression

ABSTRACT We recently found that the Gac DNA-binding protein of Borrelia burgdorferi, the Lyme disease bacterium, functions as a transcriptional repressor of the essential ospC gene. RNA-sequencing (RNA-Seq) analyses of a gac mutant revealed that Gac impacts levels of transcripts of several other virulence-associated proteins, including the alternative sigma factors RpoN and RpoS. Prior studies demonstrated that RpoN is required for expression of RpoS, and both are required for mammalian infection. The planned studies will further investigate the functions of Gac in the Lyme disease spirochete, including its impacts on mammalian and tick infection and molecular characterization of Gac's impacts on rpoN expression. Results of these studies will provide important insights on regulatory mechanisms that control virulence of the Lyme disease spirochete and help identify key components for development of improved, specific antibacterials.