Mechanisms of LuxR transcriptional regulation of quorum sensing genes
V. harveyi LuxR is the founding member of the group of transcription factors that control quorum sensing in all vibrios. LuxR shares high amino acid identity with other LuxR proteins: 71% with HapR (Vibrio cholerae), 96% with OpaR (Vibrio parahaemolyticus), and 93% with SmcR (Vibrio vulnificus). LuxR is a unique member of the TetR family of transcription factors that both activates and represses a regulon of >600 genes through binding to a degenerate consensus DNA binding motif. There is currently a gap in existing knowledge of TetR regulatory mechanisms because LuxR is the only known TetR protein that activates transcription. We are using a combination of structural biology, biochemistry, and genetics to determine how LuxR functions as an activator and a repressor of quorum-sensing genes.
Quorum-sensing regulation of group behaviors in vibrios
Among the >600 genes controlled by quorum sensing through LuxR are genesrequiredfor type III secretion, type VI secretion, motility, and osmotic stress regulation. We are interested in the patterns of gene expression that control these important physiological outputs. LuxR,AphA, and theQrrsare the central regulators of these expression patterns, though other downstream transcription factors also play important roles. Using bacterial genetics, bioinformatics, and biochemistry, we are examining the hierarchy of gene regulation that contributes to expression of key developmental and physiological pathways invibrios.
Chemical inhibitors of quorum sensing in vibrios
As the central regulator of virulence in all pathogenicvibrios,LuxRis an excellent target for developing antibiotics. We have anon-goingcollaboration with Dr. Laura Brown (IU Chemistry) to screen for and synthesize molecules that modulateLuxRactivity. We use bothin vivoandin vitroassays toidentifymolecules anddeterminetheir mechanisms of action onLuxRproteins fromV. harveyi,V. cholerae, andV. vulnificus.
