The Pseudomonas aeruginosa Outer Membrane Permeability Barrier and How to Overcome It

2015 ◽  
pp. 95-102 ◽  
Author(s):  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Permeability Barrier ◽  
Outer Membrane Permeability

scholarly journals Desferrioxamine:gallium-pluronic micelles increase outer membrane permeability and potentiate antibiotic activity againstPseudomonas aeruginosa

2018 ◽  
Vol 54 (99) ◽  
pp. 13929-13932 ◽  
Author(s):  
Max Purro ◽  
Jing Qiao ◽  
Zhi Liu ◽  
Morgan Ashcraft ◽  
May P. Xiong
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Broad Spectrum ◽  
Antibiotic Activity ◽  
Permeability Barrier ◽  
Outer Membrane Permeability

The outer membrane ofPseudomonas aeruginosafunctions primarily as a permeability barrier and imparts a broad spectrum of intrinsic antibiotic resistance.

scholarly journals Outer Membrane Permeability Barrier in Escherichia coli Mutants That Are Defective in the Late Acyltransferases of Lipid A Biosynthesis

1999 ◽  
Vol 43 (6) ◽  
pp. 1459-1462 ◽  
Author(s):  
Martti Vaara ◽  
Marjatta Nurminen
Keyword(s):  
Escherichia Coli ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Lipid A ◽  
Enteric Bacteria ◽  
Normal Function ◽  
Permeability Barrier ◽  
Core Oligosaccharide ◽  
Hydrophobic Solutes ◽  
Outer Membrane Permeability

ABSTRACT The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that theEscherichia coli msbB mutant, which elaborates defective, penta-acylated lipid A, is practically as resistant to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control strain. The susceptibility index, i.e., the approximate ratio between the MIC for the msbB mutant and that for the parent-type control, was maximally 2.7-fold. In comparison, the rfa mutant defective in the deep core oligosaccharide part of LPS displayed indices ranging from 20 to 64. The lpxA and lpxD lipid A mutants had indices higher than 512. Furthermore, the msbBmutant was resistant to glycopeptides (vancomycin, teicoplanin), whereas the rfa, lpxA, and lpxDmutants were susceptible. The msbB htrB double mutant, which elaborates even-more-defective, partially tetra-acylated lipid A, was still less susceptible than the rfa mutant. These findings indicate that hexa-acylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.

scholarly journals Importance of Real-Time Assays To Distinguish Multidrug Efflux Pump-Inhibiting and Outer Membrane-Destabilizing Activities in Escherichia coli

2015 ◽  
Vol 197 (15) ◽  
pp. 2479-2488 ◽  
Author(s):  
Rajeev Misra ◽  
Keith D. Morrison ◽  
Hyun Jae Cho ◽  
Thanh Khuu
Keyword(s):  
Escherichia Coli ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Real Time ◽  
Efflux Pump ◽  
Membrane Integrity ◽  
Efflux Pumps ◽  
Permeability Barrier ◽  
Multidrug Efflux ◽  
Outer Membrane Permeability

ABSTRACTThe constitutively expressed AcrAB multidrug efflux system ofEscherichia colishows a high degree of homology with the normally silent AcrEF system. Exposure of a strain withacrABdeleted to antibiotic selection pressure frequently leads to the insertion sequence-mediated activation of the homologous AcrEF system. In this study, we used strains constitutively expressing either AcrAB or AcrEF from their normal chromosomal locations to resolve a controversy about whether phenylalanylarginine β-naphthylamide (PAβN) inhibits the activities of AcrAB and AcrEF and/or acts synergistically with antibiotics by destabilizing the outer membrane permeability barrier. Real-time efflux assays allowed a clear distinction between the efflux pump-inhibiting activity of PAβN and the outer membrane-destabilizing action of polymyxin B nonapeptide (PMXBN). When added in equal amounts, PAβN, but not PMXBN, strongly inhibited the efflux activities of both AcrAB and AcrEF pumps. In contrast, when outer membrane destabilization was assessed by the nitrocefin hydrolysis assay, PMXBN exerted a much greater damaging effect than PAβN. Strong action of PAβN in inhibiting efflux activity compared to its weak action in destabilizing the outer membrane permeability barrier suggests that PAβN acts mainly by inhibiting efflux pumps. We concluded that at low concentrations, PAβN acts specifically as an inhibitor of both AcrAB and AcrEF efflux pumps; however, at high concentrations, PAβN in the efflux-proficient background not only inhibits efflux pump activity but also destabilizes the membrane. The effects of PAβN on membrane integrity are compounded in cells unable to extrude PAβN.IMPORTANCEThe increase in multidrug-resistant bacterial pathogens at an alarming rate has accelerated the need for implementation of better antimicrobial stewardship, discovery of new antibiotics, and deeper understanding of the mechanism of drug resistance. The work carried out in this study highlights the importance of employing real-time fluorescence-based assays in differentiating multidrug efflux-inhibitory and outer membrane-destabilizing activities of antibacterial compounds.

scholarly journals Overcoming Iron Deficiency of anEscherichia colitonBMutant by Increasing Outer Membrane Permeability

2019 ◽  
Vol 201 (17) ◽  
Author(s):  
Nan Qiu ◽  
Rajeev Misra
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Membrane Integrity ◽  
Receptor Protein ◽  
Permeability Barrier ◽  
Prolonged Incubation ◽  
Content Type ◽  
E Coli ◽  
Outer Membrane Permeability

ABSTRACTThe intake of certain nutrients, including ferric ion, is facilitated by the outer membrane-localized transporters. Due to ferric insolubility at physiological pH,Escherichia colisecretes a chelator, enterobactin, outside the cell and then transports back the enterobactin-ferric complex via an outer membrane receptor protein, FepA, whose activity is dependent on the proton motive force energy transduced by the TonB-ExbBD complex of the inner membrane. Consequently, ΔtonBmutant cells grow poorly on a medium low in iron. Prolonged incubation of ΔtonBcells on low-iron medium yields faster-growing colonies that acquired suppressor mutations in theyejM(pbgA) gene, which codes for a putative inner-to-outer membrane cardiolipin transporter. Further characterization of suppressors revealed that they display hypersusceptibility to vancomycin, a large hydrophilic antibiotic normally precluded from enteringE. colicells, and leak periplasmic proteins into the culture supernatant, indicating a compromised outer membrane permeability barrier. All phenotypes were reversed by supplying the wild-type copy ofyejMon a plasmid, suggesting thatyejMmutations are solely responsible for the observed phenotypes. The deletion of all known cardiolipin synthase genes (clsABC) did not produce the phenotypes similar to mutations in theyejMgene, suggesting that the absence of cardiolipin from the outer membraneper seis not responsible for increased outer membrane permeability. Elevated lysophosphatidylethanolamine levels and the synthetic growth phenotype withoutpldAindicated that defective lipid homeostasis in theyejMmutant compromises outer membrane lipid asymmetry and permeability barrier to allow enterobactin intake, and that YejM has additional roles other than transporting cardiolipin.IMPORTANCEThe work presented here describes a positive genetic selection strategy for isolating mutations that destabilize the outer membrane permeability barrier ofE. coli. Given the importance of the outer membrane in restricting the entry of antibiotics, characterization of the genes and their products that affect outer membrane integrity will enhance the understanding of bacterial membranes and the development of strategies to bypass the outer membrane barrier for improved drug efficacy.

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