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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Abstract Emerging drug resistance has forced the scientific community to revisit the observational data documented in the folklore and come up with novel and effective alternatives. Candidates from eukaryotic origin including herbal products and antimicrobial peptides are finding a strategic place in the therapeutic armamentarium against infectious diseases. These agents have recently gained interest owing to their versatile applications. Present review encompasses the use of these alternative strategies in their native or designer form, alone or in conjunction with antibiotics, as possible remedial measures. Further to this, the limitations or the possible concerns associated with these options are also discussed at length.
"These processes lead to breakdown of the transmembrane potential causing leakage of cell content and finally the cell death. The mechanism of antibacterial action probably includes recognition and specific interaction with bacterial cell membranes inducing lipid clustering or lipid phase separation  . "
[Show abstract][Hide abstract] ABSTRACT: Halictine-1 (Hal-1)—a linear antibacterial dodecapeptide isolated from the venom of the eusocial bee Halictus sexcinctus—has been subjected to a detailed spectroscopic study including circular dichroism, fluorescence, and vibrational spectroscopy. We investigated Hal-1 ability to adopt an amphipathic α-helical structure upon interaction with model lipid-based bacterial membranes (phosphatidylcholine/phosphatidylglycerol-based large unilamellar vesicles and sodium dodecylsulfate micelles) and helix inducing components (trifluoroethanol). It was found that Hal-1 responds sensitively to the composition of the membrane model and to the peptide/lipid ratio. The amphipathic nature of the helical Hal-1 seems to favour flat charged surfaces of the model lipid particles over the nondirectional interaction with trifluoroethanol. Increasing fraction of polyproline II type conformation was detected at low peptide/lipid ratios.
International Journal of Spectroscopy 01/2012; 27(5-6):5-6. DOI:10.1155/2012/840956
[Show abstract][Hide abstract] ABSTRACT: Multidrug-resistant bacteria are a severe threat to public health. Conventional antibiotics are becoming increasingly ineffective as a result of resistance, and it is imperative to find new antibacterial strategies. Natural antimicrobials, known as host defence peptides or antimicrobial peptides, defend host organisms against microbes but most have modest direct antibiotic activity. Enhanced variants have been developed using straightforward design and optimization strategies and are being tested clinically. Here, we describe advanced computer-assisted design strategies that address the difficult problem of relating primary sequence to peptide structure, and are delivering more potent, cost-effective, broad-spectrum peptides as potential next-generation antibiotics.
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