Broad Specificity Efflux pumps and Their Role in Multidrug Resistance of Gram Negative Bacteria
By H. Nikaido, J. Pagés. FEMS Microbiology Reviews, 2011
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Antibiotic resistance mechanisms reported in Gram-negative bacteria are producing a worldwide health problem. The continuous dissemination of «multi-drug resistant» (MDR) bacteria drastically reduces the efficacy of our antibiotic “arsenal” and consequently increases the frequency of therapeutic failure. In MDR bacteria, the over-expression 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 indicate 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 level, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may open the way to rationally develop an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms.
Subfields: Molecular Medicine, Pharmacology, Pollution
View Paper: https://www.semanticscholar.org/paper/08d6ae2361da55d209aa2878ff707b0de2431891
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Citations in the corpus
- Antimicrobial Resistance: A Growing Serious Threat for Global Public Health (2023, background): “It is interesting to note that the majority of efflux systems engage in multidrug efflux mechanisms that are always chromosomally encoded to ensure bacterial intrinsic drug resistance [48].”