Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 13, Issue 24, Pages 3079-3100Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/15680266113136660220
Keywords
Multi-drug resistance; membrane barrier; efflux pumps; RND transporters; proton motive force; AcrAB-TolC; antibiotics; EPIs
Categories
Funding
- Innovative Medicines Joint Undertaking [115525]
- European Union
- CINECA (Bologna, Italy) [Pra04_774]
- ISCRA-A [HP10ARSZ26, HP10ARS6ZX, HP10ANF5M6]
- Lawrence Berkeley National Laboratory (Berkeley, CA)
- Innovative Medicines Initiative (IMI)
- DFG [EXC115]
- Deutsche Forschungsgemeinschaft [SFB 807]
- Europe Advancing Science through Pfizer - Investigator Research Exchange (ASPIRE)
- Human Frontier Science Program
- Funding Program for Next Generation World-Leading Researchers from Japan Society for the Promotion Science
- ERATO Murata Lipid Active Structure Project
- Japan Science and Technology Agency
- Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation (NIBIO), Japan
- Human Frontier Science Program (HFSP)
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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.
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