Identification of the Pseudomonas aeruginosa AgtR-CspC-RsaL pathway that controls Las quorum sensing in response to metabolic perturbation and Staphylococcus aureus.

Environmental metabolites and metabolic pathways significantly influence bacterial pathogenesis and interspecies competition. We previously discovered that a mutation in the triosephosphate isomerase gene, tpiA, in Pseudomonas aeruginosa led to defective type III secretion and increased susceptibility to aminoglycoside antibiotics. In this study, we found that the tpiA mutation enhances the Las quorum sensing system due to reduced translation of the negative regulator RsaL. Further investigations demonstrated an upregulation of CspC, a CspA family protein that represses rsaL translation. DNA pull-down assay, along with genetic studies, revealed the role of AgtR in regulating cspC transcription. AgtR is known to regulate pyocyanin production in response to N-acetylglucosamine (GlcNAc), contributing to competition against Staphylococcus aureus. We demonstrated that CspC activates the Las quorum sensing system and subsequent pyocyanin production in response to GlcNAc and S. aureus. Overall, our results elucidate the AgtR-CspC-RsaL-LasI pathway that regulates bacterial virulence factors and its role in competition against S. aureus.