Pseudomonas
aeruginosa is an opportuni st ic pathogen and displays high-level intrinsic and acquired multiple antimicrobi
al resistance. Mechanisms for such resistance are attributed by the interplay between the broad-specific multidrug efflux pumps and the low outer membrane permeability. A total of six multidrug efflux pumps, which belong to the Resista nce-Nodulation-Division (RND) superfamily, have been characterized to date in P.aeruginosa. The RND efflux systems in Gram-negative bacteria are typicall y the three-component pumps, each composed of an inner membrane transporter, an inner membrane-associated periplasmic membrane fusion protein, and an outer me mbrane efflux channel protein. Of these known pumps of P.aeruginosa, the Mex AB-OprM efflux system plays the most important role in drug resistance and show s the broadest substrate ranges that include most conventional classes of antibi otics. Regulation of these pumps is typically linked to local regulators (repres sor or activators), whose mutations or inactivation produce multiple antibio tic-resistant strains as revealed in many clinical isolates. Efflux mechanisms act together with other resistance determinants to further raise resistance leve ls. As such, the efflux pump
inhibitors are being sought to combat efflux-media ted drug resistance in order to restore antibacterial activity of antibiotics subject to efflux. Efflux reversal of fluoroquinolones in P.aeruginosa by efflux pump inhibitors has been demonstrated.