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Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier.

Authors :
Zgurskaya HI
Rybenkov VV
Krishnamoorthy G
Leus IV
Source :
Research in microbiology [Res Microbiol] 2018 Sep - Oct; Vol. 169 (7-8), pp. 351-356. Date of Electronic Publication: 2018 Feb 16.
Publication Year :
2018

Abstract

Antibiotic resistance is a serious threat to public health. Significant efforts are currently directed toward containment of the spread of resistance, finding new therapeutic options concerning resistant human and animal pathogens, and addressing the gaps in the fundamental understanding of mechanisms of resistance. Experimental data and kinetic modeling revealed a major factor in resistance, the synergy between active efflux and the low permeability barrier of the outer membrane, which dramatically reduces the intracellular accumulation of many antibiotics. The structural and mechanistic particularities of trans-envelope efflux pumps amplify the effectiveness of cell envelopes as permeability barriers. An important feature of this synergism is that efflux pumps and the outer membrane barriers are mechanistically independent and select antibiotics based on different physicochemical properties. The synergism amplifies even weak polyspecificity of multidrug efflux pumps and creates a major hurdle in the discovery and development of new therapeutics against Gram-negative pathogens.<br /> (Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Details

Language :
English
ISSN :
1769-7123
Volume :
169
Issue :
7-8
Database :
MEDLINE
Journal :
Research in microbiology
Publication Type :
Academic Journal
Accession number :
29454787
Full Text :
https://doi.org/10.1016/j.resmic.2018.02.002