Systems-level exploitation of OxyR regulon unravels a potential antibacterial target in Pseudomonas aeruginosa

Bacteria coordinate the response to oxidative stress through LysR-type transcriptional regulator (LTTR) OxyR. However, only fragmentary information on the regulation and function of OxyR has been gleaned in the opportunistic pathogen Pseudomonas aeruginosa. Here, we delineate the OxyR regulon using multi-omics analyses. OxyR is found to positively regulate several genes involved in quorum sensing (QS) and energy metabolism. OxyR is further involved in the negative regulation of amino acid transporters that was confirmed by metabolomics analysis. Finally, we uncover gltS, an OxyR regulon gene, could be used as a potential drug potentiation target. Altogether, our results confirm that, apart from its dominant role in defense against oxidative stress in P. aeruginosa, OxyR acts as a global regulator of QS, energy metabolism and amino acid homeostasis, but also serves as a model system to identify potential antibacterial target such as gltS.