title: An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors.
abstract: Micro-organisms express a wide range of transmembrane pumps known as multidrug efflux pumps that improve the micro-organism's ability to survive in severe environments and contribute to resistance against antibiotic and antimicrobial agents. There is significant interest in developing efflux inhibitors as an adjunct to treatment with current and next generation of antibiotics. A greater understanding of drug recognition and transport by multidrug efflux pumps is needed to develop clinically useful inhibitors, given the breadth of molecules that can be effluxed by these systems. We summarize some structural and functional data that could provide insights into the inhibition of transport mechanisms of these intricate molecular nanomachines with a focus on the advances in computational approaches.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Britannia House, 7 Trinity Street, London, SE1 9NH, UK.
authors.forename: Shirin
authors.initials: S
authors.lastname: Jamshidi
authors.affiliation: Public Health England, National Infection Service, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Sutton
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Britannia House, 7 Trinity Street, London, SE1 9NH, UK.
authors.forename: Khondaker M
authors.initials: KM
authors.lastname: Rahman
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D001692:Biological Transport; D024901:Drug Resistance, Multiple, Bacterial; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D011743:Pyrimidines; C030986:pyrimidine
keywords: antimicrobial resistance; bacterial pathogenicity; computational approaches; efflux pump inhibitor; molecular dynamics; multidrug efflux pump simulation; tripartite assembly