RND Efflux Pumps: Structural Information Translated into Function and Inhibition Mechanisms

Title:RND Efflux Pumps: Structural Information Translated into Function and Inhibition Mechanisms

Volume: 13 Issue: 24

Author(s): Paolo Ruggerone, Satoshi Murakami, Klaas M. Pos and Attilio V. Vargiu

Affiliation:

Keywords: Multi-drug resistance, membrane barrier, efflux pumps, RND transporters, proton motive force, AcrAB-TolC, antibiotics, EPIs.

Abstract: 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.

Cite this article as:

Ruggerone Paolo, Murakami Satoshi, M. Pos Klaas and Vargiu V. Attilio, RND Efflux Pumps: Structural Information Translated into Function and Inhibition Mechanisms, Current Topics in Medicinal Chemistry 2013; 13 (24) . https://dx.doi.org/10.2174/15680266113136660220