Journal
FEMS MICROBIOLOGY REVIEWS
Volume 36, Issue 2, Pages 340-363Publisher
OXFORD UNIV PRESS
DOI: 10.1111/j.1574-6976.2011.00290.x
Keywords
antibiotic resistance; RND family drug transporters; bacterial efflux pump; MDR bacteria; outer membrane permeability; structure-function relationship
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Funding
- Service de Sante des Armees
- Universite de la Mediterranee
- ANR METABACT
- USPHS [AI-09644]
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Antibiotic resistance mechanisms reported in Gram-negative bacteria are causing a worldwide health problem. The continuous dissemination of multidrug-resistant (MDR) bacteria drastically reduces the efficacy of our antibiotic arsenal and consequently increases the frequency of therapeutic failure. In MDR bacteria, the overexpression of efflux pumps that expel structurally unrelated drugs contributes to the reduced susceptibility by decreasing the intracellular concentration of antibiotics. During the last decade, several clinical data have indicated an increasing involvement of efflux pumps in the emergence and dissemination of resistant Gram-negative bacteria. It is necessary to clearly define the molecular, functional and genetic bases of the efflux pump in order to understand the translocation of antibiotic molecules through the efflux transporter. The recent investigation on the efflux pump AcrB at its structural and physiological levels, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may pave the way towards the rational development of an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms.
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