Pseudomonas aeruginosa has an extraordinary capacity to evade the activity of antibiotics through a complex interplay of intrinsic and mutation-driven resistance pathways, which are, unfortunately, often additive or synergistic, leading to multidrug (or even pandrug) resistance. However, we show that one of these mechanisms, overexpression of the MexCD-OprJ efflux pump (driven by inactivation o...

24 25 Constitutive overproduction of the pump MexXY/OprM (XY+/M) is recognized as a major 26 cause of resistance to aminoglycosides, fluoroquinolones, and zwitterionic cephalosporins in 27 P. aeruginosa. In this study, 57 clonally-unrelated strains recovered from non-cystic fibrosis 28 patients were analyzed to characterize the mutations resulting in upregulation of the mexXY 29 operon. Forty f...

Pan-aminoglycoside-resistant Pseudomonas aeruginosa mutants expressing the mexXY components of the aminoglycoside-accommodating MexXY-OprM multidrug efflux system but lacking mutations in the mexZ gene encoding a repressor of this efflux system and in the mexXY promoter have been reported (S. Fraud and K. Poole, Antimicrob. Agents Chemother. 55:1068-1074, 2011). Genome sequencing of one of thes...

Drug efflux systems contribute to the intrinsic resistance of Pseudomonas aeruginosa to many antibiotics and biocides and hamper research focused on the discovery and development of new antimicrobial agents targeted against this important opportunistic pathogen. Using a P. aeruginosa PAO1 derivative bearing deletions of opmH, encoding an outer membrane channel for efflux substrates, and four ef...