The Transcriptional Regulator BpsR Controls the Growth ofBordetella bronchisepticaby Repressing Genes Involved in Nicotinic Acid Degradation
ABSTRACTMany of the pathogenic species of the genusBordetellahave an absolute requirement for nicotinic acid (NA) for laboratory growth. These Gram-negative bacteria also harbor a gene cluster homologous to theniccluster ofPseudomonas putidawhich is involved in the aerobic degradation of NA and its transcriptional control. We report here that BpsR, a negative regulator of biofilm formation and Bps polysaccharide production, controls the growth ofBordetella bronchisepticaby repressing the expression ofnicgenes. The severe growth defect of the ΔbpsRstrain in Stainer-Scholte medium was restored by supplementation with NA, which also functioned as an inducer ofnicgenes at low micromolar concentrations that are usually present in animals and humans. Purified BpsR protein bound to thenicpromoter region, and its DNA binding activity was inhibited by 6-hydroxynicotinic acid (6-HNA), the first metabolite of the NA degradative pathway. Reporter assays with the isogenic mutant derivative of the wild-type (WT) strain harboring deletion innicA, which encodes a putative nicotinic acid hydroxylase responsible for conversion of NA to 6-HNA, showed that 6-HNA is the actual inducer of thenicgenes in the bacterial cell. Gene expression profiling further showed that BpsR dually activated and repressed the expression of genes associated with pathogenesis, transcriptional regulation, metabolism, and other cellular processes. We discuss the implications of these findings with respect to the selection of pyridines such as NA and quinolinic acid for optimum bacterial growth depending on the ecological niche.IMPORTANCEBpsR, the previously described regulator of biofilm formation and Bps polysaccharide production, controlsBordetella bronchisepticagrowth by regulating the expression of genes involved in the degradation of nicotinic acid (NA). 6-Hydroxynicotinic acid (6-HNA), the first metabolite of the NA degradation pathway prevented BpsR from binding to DNA and was the actualin vivoinducer. We hypothesize that BpsR enablesBordetellabacteria to efficiently and selectively utilize NA for their survival depending on the environment in which they reside. The results reported herein lay the foundation for future investigations of how BpsR and the alteration of its activity by NA orchestrate the control ofBordetellagrowth, metabolism, biofilm formation, and pathogenesis.