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

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.81). 07/2011; 68(13):2177-88. DOI: 10.1007/s00018-011-0711-9
Source: PubMed


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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    • "PEG-PE is a lipid anchored hydrophilic flexible polymer that has been shown to reduce the clearance of liposomes by reticulo-endothelial system. Some antimicrobial agents that cluster anionic lipids can also form cochleate structures when complexed with lipid mixtures (Epand et al., 2011). Cochleates can both entrap other drugs and can facilitate drug delivery by protecting these drugs from enzymes in the serum and they can also effectively deliver drug to tissues. "
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