RND Efflux Pumps: Structural Information Translated into Function and Inhibition Mechanisms
Klaas M. Pos,
Attilio V. Vargiu.
Efflux pumps of the Resistance Nodulation Division (RND) superfamily play a major role in the intrinsic and
acquired resistance of Gram-negative pathogens to antibiotics. Moreover, they are largely responsible for multi-drug resistance
(MDR) phenomena in these bacteria. The last decade has seen a sharp increase in the number of experimental and
computational studies aimed at understanding their functional mechanisms. Most of these studies focused on the RND
drug/proton antiporter AcrB, part of the AcrAB-TolC efflux pump actively recognizing and expelling noxious agents from
the interior of bacteria. These studies have been focused on the dynamical interactions between AcrB and its substrates
and inhibitors, on the details of the proton translocation mechanisms, and on the way AcrB assembles with protein partners
to build up a functional pump. In this review we summarize these advances focusing on the role of AcrB.
Keywords: Multi-drug resistance, membrane barrier, efflux pumps, RND transporters, proton motive force, AcrAB-TolC, antibiotics,
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