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

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.

Cochleate characterization by cryogenic electron microscopy methods: Cryo-TEM and Cryo-SEM

“…However, although the whole shape may be identified [42,43], the details are at low resolution and not sufficient to differentiate between cochleates, tubules, or other elongated structures. Hence, it may be suggested to use light microscopy mainly for screening for cochleates as a step before further investigation by EM methods.…”

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

“…We therefore chose the option to protect the susceptible points of proteolysis of the molecule. Other options may increase the stability such as polyethyleneglycol (PEG) [31], the use of lipids for drug delivery of the peptides [32], the use of nanoparticules in order to achieve a longer life time [33] or the use of dendrimers [34]. The mastoparan family is a very promising group of potential new drugs.…”

Dispersion and stabilization of cochleate nanoparticles

“…shown their applicability as vaccine adjuvants [4][5][6][7][8] and carriers of antibiotics [9][10][11][12], systemic antimycotic agents [13][14][15][16] or factor VII for replacement in hemophilia A [17,18].…”