Open AccessBroad‐specificity efflux pumps and their role in multidrug resistance of Gram‐negative bacteria
Author(s) -
Nikaido Hiroshi,
Pagès JeanMarie
Publication year - 2012
Publication title -
fems microbiology reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.91
H-Index - 212
eISSN - 1574-6976
pISSN - 0168-6445
DOI - 10.1111/j.1574-6976.2011.00290.x
Subject(s) - efflux , antibiotics , bacteria , biology , multiple drug resistance , gram negative bacteria , microbiology and biotechnology , antibiotic resistance , drug resistance , transporter , biochemistry , genetics , escherichia coli , gene
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.