MexAB-OprM efflux pump regulatory proteins (MexAB-OprM regulators)

The MexAB-OprM efflux pump regulatory proteins, primarily MexR, NalC, and NalD, are transcriptional regulators in Pseudomonas aeruginosa that control the expression of the MexAB-OprM multidrug efflux system (Li et al., 2015, Clinical Microbiology Reviews). MexR acts as the primary repressor by binding to the promoter of the mexAB-oprM operon, while NalD serves as a secondary repressor that binds to a distinct promoter site (Poole et al., 1996, Antimicrobial Agents and Chemotherapy; Chen et al., 2016, FEBS Letters). NalC indirectly regulates the system by repressing the armR gene; mutations in nalC lead to the production of ArmR, an anti-repressor that binds to MexR and prevents it from inhibiting the efflux pump (Sobel et al., 2005, Antimicrobial Agents and Chemotherapy). Mutations in these regulatory proteins are a major driver of constitutive pump overexpression in clinical isolates, leading to multidrug resistance against various antibiotics, including beta-lactams, fluoroquinolones, and carbapenems. These regulatory proteins are significant therapeutic targets for the development of efflux pump inhibitors (EPIs) or resistance-breakers designed to restore the efficacy of conventional antibiotics against resistant P. aeruginosa infections.

Other names

MexRNalCNalDPA0424PA3721PA3574MexAB-OprM operon regulators

Efflux pump inhibition and restoration of antibiotic sensitivity by modulating the expression or activity of the MexAB-OprM system.