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Trends Mol Med. 2005 Aug;11(8):382-9.

Inhibitors of efflux pumps in Gram-negative bacteria.

Author information

1
EA2197, IFR48, Faculté de Médecine, Université de la Méditerranée, 13385-Marseille, France. Jean-Marie.Pages@medecine.univ-mrs.fr

Abstract

In Gram-negative bacteria, efflux complexes, consisting of an inner-membrane pump, a periplasmic adaptor protein and outer-membrane channel, provide an efficient means for the export of structurally unrelated drugs, causing the multidrug-resistance phenotype. Resistance due to this antibiotic efflux is an increasing problem worldwide. A new molecular challenge is to combat this transport by searching for new molecules to block efflux and thus restore drug susceptibility to resistant clinical strains. Recent data shed new light on the structure and activity of the archetypal efflux pumps AcrAB-TolC and MexAB-OprM. Here, we describe recent insights into the molecular mechanisms of bacterial efflux pumps and their inhibitors. Current progress for the clinical use of efflux-pump inhibitors and new strategies to combat the drug-efflux mechanisms will be discussed.

PMID:
15996519
DOI:
10.1016/j.molmed.2005.06.006
[Indexed for MEDLINE]

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