Transcriptional Regulation of Carnitine Catabolism in Pseudomonas aeruginosa by CdhR

The common environmental bacterium and opportunistic pathogen Pseudomonas aeruginosa encodes diverse metabolic pathways and associated regulatory networks allowing it to thrive in these different environments. In an effort to understand P. aeruginosa metabolism and detection of host-derived compounds, we previously identified CdhR and GbdR as members of the AraC transcription factor family that regulate catabolism of the quaternary amine compounds carnitine and glycine betaine, respectively. In this study, our goal was to further characterize regulation of carnitine catabolism by the transcription factor CdhR. CdhR binds in a concentration-dependent manner upstream of the carnitine catabolism operon promoter (P(caiXcdhCABhocS)). We identified the CdhR binding site and determined that it overlaps with the GbdR binding site in the caiX-cdhR intergenic region. Carnitine catabolism is repressed by glucose and glycine betaine, and here we show this happens at the transcriptional level. Furthermore, we show that CdhR enhances its own expression and that GbdR contributes to cdhR expression by enhancing the level of basal expression. The intertwined regulation of caiX and cdhR transcription by GbdR and CdhR suggests that carnitine catabolism is under tight but tuneable control. IMPORTANCE Pathogens must metabolize host-derived compounds during infection and properly regulate the responsible pathways. Carnitine is a common eukaryotic-associated quaternary amine compound that can be catabolized by Pseudomonas aeruginosa. Here we expand on our understanding of how this metabolic pathway is regulated and provide details on how carnitine catabolism is intertwined with glycine betaine catabolism at the level of transcriptional control.