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Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents

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Abstract

Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance.

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Abbreviations

ABC:

ATP-binding cassette

DMPC:

Dimyristoyl phosphatidylcholine

DMPG:

Dimyristoyl phosphatidylglycerol

DMPE:

Dimyristoyl phosphatidylethanolamine

DOPE:

Dioleoyl phosphatidylethanolamine

DOPS:

Dioleoyl phosphatidylserine

EM:

Electron microscopy

MDR:

Multidrug resistant

MIC:

Minimum inhibitory concentration

MLVs:

Multilamellar vesicles

OAK:

Oligo-acyl-lysine

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PEG-PE:

Polyethylene glycol linked covalently to the amino group of PE

POPE:

1-palmitoyl-2-oleoyl phosphatidylethanolamine

PS:

Phosphatidylserine

RND:

Resistance-nodulation-division

TMCL:

Tetramyristoyl cardiolipin

TOCL:

Tetraoleoyl cardiolipin

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Authors and Affiliations

  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada

    Raquel F. Epand & Richard M. Epand

  2. Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, 32000, Haifa, Israel

    Amram Mor

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  1. Raquel F. Epand
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Epand, R.F., Mor, A. & Epand, R.M. Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents. Cell. Mol. Life Sci. 68, 2177–2188 (2011). https://doi.org/10.1007/s00018-011-0711-9

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