Catabolite Activator Protein and quorum sensing cross-control group behaviors in Vibrio campbellii

Vibrio species adapt to different niches by sensing and responding to environmental signals such as nutrients, host cues, and quorum sensing autoinducers. Vibrio campbellii uses the master quorum sensing transcription factor LuxR to control expression of hundreds of genes at high cell density. Furthermore, many gamma-proteobacteria use the global transcription factor Catabolite Activator Protein (CAP) to control numerous physiologically relevant pathways, many of which are also modulated by quorum sensing, such as competence, biofilm formation, and carbon metabolism. However, the extent to which these two global transcription factors overlap to co-regulate gene expression and bacterial behaviors is understudied. In this work, we used ChIP-seq and RNA-seq to determine the individual and combined regulons of CAP and LuxR in V. campbellii . We found that CAP and LuxR co-occupied 11 promoters to synergistically or antagonistically co-regulate genes involved with metabolism, respiration, and virulence. It was previously proposed that CAP and LuxR both bound the bioluminescence ( luxCDABE ) promoter to co-regulate these genes, and our RNA-seq data showed that these were indeed the most strongly co-regulated genes. However, our ChIP-seq data revealed that only LuxR bound the luxCDABE promoter in vivo . This pattern of co-regulation—where both CAP and LuxR strongly impact transcription but only LuxR binds the promoter—was the most common mechanism observed. Our model for bioluminescence regulation is that CAP indirectly activates luxCDABE expression through the regulation of an intermediate factor. This study established new connections between the global gene regulatory networks underpinning nutrient sensing and population sensing.