Bacterial resistance to antibiotics: Active efflux and reduced uptake

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339 Scopus citations

Abstract

Antibiotic resistance of bacterial pathogens is a fast emerging global crisis and an understanding of the underlying resistance mechanisms is paramount for design and development of new therapeutic strategies. Permeability barriers for and active efflux of drug molecules are two resistance mechanisms that have been implicated in various infectious outbreaks of antibiotic-resistant pathogens, suggesting that these mechanisms may be good targets for new drugs. The synergism of reduced uptake and efflux is most evident in the multiplicative action of the outer membrane permeability barrier and active efflux, which results in high-level intrinsic and/or acquired resistance in many clinically important Gram-negative bacteria. This review summarizes the current knowledge of these two important resistance mechanisms and potential strategies to overcome them. Recent advances in understanding the physical structures, function and regulation of efflux systems will facilitate exploitation of pumps as new drug targets.

Original languageEnglish (US)
Pages (from-to)1486-1513
Number of pages28
JournalAdvanced Drug Delivery Reviews
Volume57
Issue number10
DOIs
StatePublished - Jul 29 2005
Externally publishedYes

Keywords

  • Active efflux
  • Outer membrane permeability
  • Porins
  • Regulation
  • RND pumps

ASJC Scopus subject areas

  • Pharmaceutical Science

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