Antimicrobial resistance represents a significant challenge to future healthcare provision. An acronym ESKAPEE has been derived from the names of the organisms recognised as the major threats although there are a number of other organisms, notably Neisseria gonorrhoeae, that have become equally challenging to treat in the clinic. These pathogens are characterised by the ability to rapidly develop and/or acquire resistance mechanisms in response to exposure to different antimicrobial agents. A key part of the armoury of these pathogens is a series of efflux pumps, which effectively exclude or reduce the intracellular concentration of a large number of antibiotics, making the pathogens significantly more resistant. These efflux pumps are the topic of considerable interest, both from the perspective of basic understanding of efflux pump function, and its role in drug resistance but also as targets for the development of novel adjunct therapies. The necessity to overcome antimicrobial resistance has encouraged investigations into the characterisation of resistance-modifying efflux pump inhibitors to block the mechanisms of drug extrusion, thereby restoring antibacterial susceptibility and returning existing antibiotics into the clinic. 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. This review discusses different bacterial EPIs originating from both natural source and chemical synthesis and examines the challenges to designing successful EPIs that can be useful against multidrug resistant bacteria.
Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps
Hannah Y. Mahmood,S. Jamshidi,J. Sutton,K. Rahman
Published 2016 in Current Medicinal Chemistry
ABSTRACT
PUBLICATION RECORD
- Publication year
2016
- Venue
Current Medicinal Chemistry
- Publication date
2016-02-29
- Fields of study
Biology, Medicine, Chemistry
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- chemical synthesis
Laboratory-based compound production used as a source of synthetic efflux pump inhibitors.
Aliases: synthetic chemistry
- drug extrusion
The active removal of antimicrobial compounds from bacterial cells by efflux machinery.
Aliases: drug export
- drug recognition and transport
The binding and translocation steps by which an efflux pump identifies and moves substrates across the membrane.
Aliases: substrate recognition and transport
- efflux pump inhibitors
Compounds that block bacterial efflux pumps and reduce export of antimicrobial agents from cells.
Aliases: EPI, EPIs
- multidrug efflux pumps
Bacterial membrane transport systems that export many structurally diverse compounds, including antibiotics.
Aliases: efflux pumps, multidrug efflux systems
- natural source
A biological or environmental origin for compounds discussed as sources of efflux pump inhibitors.
Aliases: natural sources