Multidrug resistance protein MexY (MexY) (MexY)

Multidrug resistance protein MexY (MexY) is a critical inner membrane transporter component of the MexXY-OprM efflux system in Pseudomonas aeruginosa, belonging to the Resistance-Nodulation-Division (RND) family (UniProt: P52478). It is primarily responsible for the efflux of a wide range of antibiotics, most notably aminoglycosides, but also tetracyclines, macrolides, and some fluoroquinolones (Westbrock-Wadman et al., 1999, PubMed: 10516754). MexY works as part of a tripartite complex where it captures substrates and, with the help of the adapter protein MexX, delivers them to the outer membrane porin OprM for extrusion into the extracellular space. The expression of the mexY gene is typically regulated by the repressor MexZ; however, mutations in mexZ or other regulatory pathways often lead to the constitutive overexpression of MexY, resulting in high-level multidrug resistance (Llanes et al., 2011, PubMed: 25645828). This resistance mechanism is a major clinical challenge in treating chronic Pseudomonas infections, particularly in patients with cystic fibrosis. Consequently, MexY is a significant target for the development of efflux pump inhibitors (EPIs) designed to restore antibiotic susceptibility in resistant strains. Research into MexY inhibitors aims to enhance the efficacy of existing antimicrobial therapies by blocking the primary escape route for these drugs.

Other names

MexYRND efflux transporter MexYPA2018Multidrug resistance protein MexY

MexY acts as the substrate-recognition and energy-coupling component of the MexXY-OprM efflux pump. It utilizes the proton motive force to drive the active transport of antibiotics from the periplasm or cytoplasm through the MexX adapter to the OprM exit duct (Morita et al., 2001, PubMed: 11133754).