期刊
CURRENT MEDICINAL CHEMISTRY
卷 18, 期 19, 页码 2969-2980出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986711796150469
关键词
Antibiotic; antibacterial agent; bacterial transporter; chemosensitizer; efflux pump; efflux pump inhibitor; drug transporter; Gram-negative bacteria; genetic regulation cascade; membrane permeability; multidrug resistance
资金
- COST Action [BM0701]
- Universite de la Mediterranee
- Service de Sante des Armees
The worldwide dissemination of multi-drug resistant (MDR) pathogens has severely reduced the efficacy of our antibiotic arsenal and increased the frequency of therapeutic failure. MDR bacteria over-express efflux pumps and this active mechanism can extrude all classes of antibiotics from the cell. It is necessary to clearly decipher the genetic, structural and functional aspects of this transport system in order to combat this poly-selective mechanism. By understanding how efflux pumps work we may be able to develop a new group of antibacterial agents, collectively termed efflux reversals, including membrane permeabilisers, efflux pump inhibitors and flux-competitive agents, specific blockers, energy poisons, etc. Several chemical families of efflux pump inhibitors have been described and characterized. Among them several inhibitor compounds demonstrate efficient blocking of the efflux pump activity involved in the MDR phenotype as observed in many Gram-negative clinical isolates. This new family of molecules represents the first antibacterial class of compound specifically targeting active transport in the bacterial cell.
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