Elucidating the Sensing Abilities of Virulence Regulatory Systems

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PROJECT SUMMARY Bacterial pathogens exert tight control over their proteomes. This proposal examines how Salmonella enterica serovar Typhimurium exerts this control. It makes direct use of novel methods and conceptual breakthroughs developed during the last grant period. First, we will identify genes that govern global DNA supercoiling using Fluorescence Evaluation of DNA Supercoiling, a novel high throughput method that examines DNA supercoiling in living cells. We will then investigate how the identified genes control this essential process. Second, we will explore the mechanism by which the master virulence regulator PhoP promotes transcription of an open reading frame when binding to that very same open reading frame. These unusually located PhoP binding sites were uncovered with Identification of Transcription Factor Sites, a novel algorithm that captures transcription factor binding sites genome wide and overcomes the limitations of SELEX and ChIP-seq. And third, we will determine the post- transcriptional mechanisms by which the RNA chaperone CspC and the novel small protein UgtS control the abundance and activity of the virulence protein UgtL. The proposed research will provide a molecular understanding of cellular physiology and likely be broadly applicable because all bacteria supercoil their DNA, activate gene transcription, and exert post-transcriptional control of their genes.