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Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier.
- 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.)
- Subjects :
- Anti-Bacterial Agents pharmacology
Bacterial Outer Membrane Proteins genetics
Bacterial Proteins genetics
Biological Transport
Gram-Negative Bacteria drug effects
Gram-Negative Bacteria genetics
Membrane Transport Proteins genetics
Anti-Bacterial Agents metabolism
Bacterial Outer Membrane Proteins metabolism
Bacterial Proteins metabolism
Gram-Negative Bacteria metabolism
Membrane Transport Proteins metabolism
Subjects
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