Multidrug resistance protein MexY (MexY)

Multidrug resistance protein MexY is a key component of the MexXY-OprM efflux system in Pseudomonas aeruginosa, a major opportunistic pathogen. As a member of the Resistance-Nodulation-Division (RND) family, MexY serves as the cytoplasmic membrane transporter that recognizes and expels a wide range of antibiotics, including aminoglycosides, macrolides, and fluoroquinolones [1][2]. The mexY gene is part of the mexXY operon, which is frequently overexpressed in multidrug-resistant clinical strains, especially in the context of chronic respiratory infections like cystic fibrosis [2][3]. This efflux activity significantly decreases the intracellular accumulation of drugs, thereby conferring high-level resistance and complicating therapeutic interventions. Because of its central role in antibiotic evasion, MexY is considered a high-priority target for the development of efflux pump inhibitors (EPIs) designed to potentiate the activity of co-administered antibiotics [1][4]. These inhibitors aim to block the pump's mechanism, effectively trapping the antibiotic inside the bacterial cell to reach its lethal concentration. Research into MexY also focuses on its unique ability to transport aminoglycosides, a trait not shared by many other RND pumps in P. aeruginosa [2]. Understanding the structural basis of MexY substrate specificity is crucial for designing next-generation antimicrobials that can bypass this resistance mechanism. Sources: [1] UniProt Consortium. UniProtKB - P52003 (MEXY_PSEAE). https://www.uniprot.org/uniprotkb/P52003/entry [2] Morita Y, Tomida J, Kawamura Y. MexXY multidrug efflux system of Pseudomonas aeruginosa. Front Microbiol. 2012;3:408. https://pubmed.ncbi.nlm.nih.gov/23226144/ [3] Poole K. Efflux-mediated resistance to fluoroquinolones in Gram-negative bacteria. Antimicrob Agents Chemother. 2000;44(9):2233-2241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90055/ [4] Lomovskaya O, Watkins WJ. Inhibition of efflux pumps: role in drug discovery. Chem Rev. 2001;101(10):2801-2814. https://pubmed.ncbi.nlm.nih.gov/11749388/

Other names

MexYRND efflux transporter MexYAminoglycoside resistance protein MexYResistance-Nodulation-Division efflux pump subunit MexY

Efflux pump inhibition to restore antibiotic sensitivity and increase intracellular drug accumulation.