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  • Title: Bacterial efflux pump inhibition.
    Author: Kaatz GW.
    Journal: Curr Opin Investig Drugs; 2005 Feb; 6(2):191-8. PubMed ID: 15751743.
    Abstract:
    Drug efflux is recognized as a clinically relevant mechanism of antimicrobial drug resistance in selected species of bacteria. Membrane-based polypeptides belong to distinct protein superfamilies, the members of which are related by structural characteristics, mechanism of action and energy source for the transport process. These membrane-based polypeptides mediate drug efflux, and some of these proteins, the multidrug efflux proteins, are capable of extruding numerous structurally dissimilar antimicrobial agents and biocides. Inhibition of these pumps can decrease intrinsic resistance, reverse acquired resistance and reduce the emergence of mutants with higher-level target-based mutational resistance. In vitro and limited in vivo investigations have shown that combining efflux pump inhibitors with antimicrobial agents that are pump substrates can result in the recovery of clinically relevant activity of those compounds. The identification of broad-spectrum efflux pump inhibitors may reduce the need, and thus cost, of discovery and development of new antimicrobial agents that are not pump substrates.
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