Abstract
The emergence of microbes resistant to conventional antibiotics is a burgeoning threat to humanity with significant impacts on the health of people and on the health system itself. Antimicrobial peptides (AMPs) hold promise as potential future alternatives to conventional drugs because they form an integral part of the defense systems of other species in the animal, plant, and fungal kingdoms. To aid the design of the next generation of AMPs optimized for human use, we must first understand the mechanism of action of existing AMPs with their targets, ideally in the context of the complex landscape of the living (microbial) cell. Advances in lasers, optics, detectors, fluid dynamics and various probes has enabled the experimentalist to measure the kinetics of molecule–membrane, molecule–molecule, and molecule–cell interactions with increasing spatial and temporal resolution. The purpose of this review is to highlight studies into these dynamic interactions with a view to improving our understanding of AMP mechanisms.
Highlights
Antimicrobial peptides (AMPs) are part of the innate immune defense system of many organisms in the animal, plant, and fungal kingdoms [1]
Of the 3,000 or so AMPs so far isolated from nature, only a relatively small number of structures have been obtained by high-resolution x-ray or NMR spectroscopy in a membrane environment [2,3,4,5,6,7,8]
I have attempted to provide a flavor of the range of dynamics AMPs undergo when presented with membranes, cells and cell populations
Summary
Antimicrobial peptides (AMPs) are part of the innate immune defense system of many organisms in the animal, plant, and fungal kingdoms [1]. Of the 3,000 or so AMPs so far isolated from nature, only a relatively small number of structures have been obtained by high-resolution x-ray or NMR spectroscopy in a membrane environment [2,3,4,5,6,7,8] These seminal structural studies have revealed that some AMPs can form pores and/or channels in membranes, disrupting the barrier function of the membrane essential to the life of the cell. Biophysical studies on other classes of AMPs with model membranes have revealed alternative structures where peptides reside on the surface of the membrane, as opposed to passing through it in a transmembrane pore This has led to alternative membrane-disruption mechanisms, as in the carpet model [9]. A common theme to all the models seems to be some sort of AMP-induced perturbation or disruption of the membrane, either transient, permanent, or both
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