Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria
- PMID: 12022261
- DOI: 10.2174/1389201023378454
Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria
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.
Similar articles
-
Synergy between Active Efflux and Outer Membrane Diffusion Defines Rules of Antibiotic Permeation into Gram-Negative Bacteria.mBio. 2017 Oct 31;8(5):e01172-17. doi: 10.1128/mBio.01172-17. mBio. 2017. PMID: 29089426 Free PMC article.
-
[The role of cell wall organization and active efflux pump systems in multidrug resistance of bacteria].Mikrobiyol Bul. 2007 Apr;41(2):309-27. Mikrobiyol Bul. 2007. PMID: 17682720 Review. Turkish.
-
Multidrug resistance mechanisms: drug efflux across two membranes.Mol Microbiol. 2000 Jul;37(2):219-25. doi: 10.1046/j.1365-2958.2000.01926.x. Mol Microbiol. 2000. PMID: 10931319 Review.
-
Understanding efflux in Gram-negative bacteria: opportunities for drug discovery.Expert Opin Drug Discov. 2012 Jul;7(7):633-42. doi: 10.1517/17460441.2012.688949. Epub 2012 May 19. Expert Opin Drug Discov. 2012. PMID: 22607346 Review.
-
Mechanism of antibiotic efflux in Gram-negative bacteria.Front Biosci. 2003 Sep 1;8:s862-73. doi: 10.2741/1134. Front Biosci. 2003. PMID: 12957812 Review.
Cited by
-
Microbe-host interactions: structure and role of Gram-negative bacterial porins.Curr Protein Pept Sci. 2012 Dec;13(8):843-54. doi: 10.2174/138920312804871120. Curr Protein Pept Sci. 2012. PMID: 23305369 Free PMC article. Review.
-
Differential impact of MexB mutations on substrate selectivity of the MexAB-OprM multidrug efflux pump of Pseudomonas aeruginosa.J Bacteriol. 2004 Mar;186(5):1258-69. doi: 10.1128/JB.186.5.1258-1269.2004. J Bacteriol. 2004. PMID: 14973037 Free PMC article.
-
Pathogenesis of the Pseudomonas aeruginosa Biofilm: A Review.Pathogens. 2022 Feb 27;11(3):300. doi: 10.3390/pathogens11030300. Pathogens. 2022. PMID: 35335624 Free PMC article. Review.
-
Cell-mediated drug delivery.Expert Opin Drug Deliv. 2011 Apr;8(4):415-33. doi: 10.1517/17425247.2011.559457. Epub 2011 Feb 24. Expert Opin Drug Deliv. 2011. PMID: 21348773 Free PMC article. Review.
-
Defects in Efflux (oprM), β-Lactamase (ampC), and Lipopolysaccharide Transport (lptE) Genes Mediate Antibiotic Hypersusceptibility of Pseudomonas aeruginosa Strain Z61.Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00784-19. doi: 10.1128/AAC.00784-19. Print 2019 Jul. Antimicrob Agents Chemother. 2019. PMID: 31036686 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
