Abstract
Intrinsic and acquired multidrug resistance in Gram-negative bacteria owes much to the synergy between limited outer membrane permeability and energy-dependent multidrug efflux. The importance of the outer membrane vis-a-vis resistance is aptly demonstrated by the impact of mutational changes in outer membrane constituents on drug susceptibility. Changes in lipopolysaccharide (LPS) that correlate with increased drug susceptibility confirm, for example, the significance of this macromolecule in the intrinsic antimicrobial resistance of Gram-negative bacteria. Alterations in LPS and porins correlating with increased resistance to a variety of antimicrobials are also known and highlight the significance of the outer membrane vis-a-vis acquired antimicrobial resistance. Efflux systems accommodating a range of structurally distinct antimicrobials, including antibiotics, detergents, dyes, biocides and aromatic hydrocarbons have been identified in a number of Gram-negative organisms. Mutational studies have confirmed the importance of these systems to intrinsic and acquired antimicrobial resistance in important disease-causing organisms. As such, strategies aimed at thwarting efflux and or the outer membrane barrier are effective at reversing antimicrobial resistance in these organisms.
Keywords: mdr, multidrug efflux, antimicrobial resistance, rnd-mfp-omf
Current Pharmaceutical Biotechnology
Title: Outer Membranes and Efflux: The Path to Multidrug Resistance in Gram- Negative Bacteria
Volume: 3 Issue: 2
Author(s): Keith Poole
Affiliation:
Keywords: mdr, multidrug efflux, antimicrobial resistance, rnd-mfp-omf
Abstract: Intrinsic and acquired multidrug resistance in Gram-negative bacteria owes much to the synergy between limited outer membrane permeability and energy-dependent multidrug efflux. The importance of the outer membrane vis-a-vis resistance is aptly demonstrated by the impact of mutational changes in outer membrane constituents on drug susceptibility. Changes in lipopolysaccharide (LPS) that correlate with increased drug susceptibility confirm, for example, the significance of this macromolecule in the intrinsic antimicrobial resistance of Gram-negative bacteria. Alterations in LPS and porins correlating with increased resistance to a variety of antimicrobials are also known and highlight the significance of the outer membrane vis-a-vis acquired antimicrobial resistance. Efflux systems accommodating a range of structurally distinct antimicrobials, including antibiotics, detergents, dyes, biocides and aromatic hydrocarbons have been identified in a number of Gram-negative organisms. Mutational studies have confirmed the importance of these systems to intrinsic and acquired antimicrobial resistance in important disease-causing organisms. As such, strategies aimed at thwarting efflux and or the outer membrane barrier are effective at reversing antimicrobial resistance in these organisms.
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Cite this article as:
Poole Keith, Outer Membranes and Efflux: The Path to Multidrug Resistance in Gram- Negative Bacteria, Current Pharmaceutical Biotechnology 2002; 3 (2) . https://dx.doi.org/10.2174/1389201023378454
DOI https://dx.doi.org/10.2174/1389201023378454 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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