MexR

MexR is a transcriptional repressor in Pseudomonas aeruginosa and related species, encoded by the mexR gene. It belongs to the MarR family of transcriptional regulators and acts as a negative regulator of the mexAB-oprM efflux pump operon, which encodes a multidrug efflux system that reduces intracellular antibiotic concentrations.

Mechanistically, MexR typically forms a dimer and binds to the promoter region of mexAB-oprM, repressing transcription and limiting pump production under baseline conditions. Repression can be relieved by environmental signals or genetic changes, leading to increased expression of the MexAB-OprM pump and enhanced efflux of a broad range of antibiotics. This process contributes to reduced susceptibility and can participate in adaptive resistance during antimicrobial exposure.

MexR is part of a broader regulatory network controlling mexAB-oprM, which also includes additional repressors such as NalC and NalD. Mutations in mexR or in these regulatory elements can derepress the operon, resulting in higher levels of the efflux pump and multidrug resistance. In clinical isolates, mexR mutations are a documented mechanism contributing to resistance against beta-lactams, fluoroquinolones, tetracyclines, and other agents.

Research and clinical implications emphasize understanding MexR function to inform strategies aimed at restoring antibiotic susceptibility. Structural and genetic studies of MexR have shed light on DNA-binding and regulatory dynamics, while explorations of efflux-pump inhibitors seek to counteract MexAB-OprM-mediated resistance.

Etymology-wise, MexR denotes the regulator of the MexA-MexB-OprM efflux system, highlighting its regulatory role within this key resistance determinant in P. aeruginosa.