State of the Art of Cyclic Lipopeptide-Membrane Interactions: Pore Formation and Bilayer Permeability.

Abstract

Background/Objectives: Resistance of pathogenic microorganisms to antibiotics poses a serious threat to public health and often leads to devastating consequences. In this context, one of the pressing challenges in pharmacochemistry is the search for new, effective antibiotics to combat severe human diseases. Cyclic lipopeptides have emerged as some of the most promising candidates and have been widely studied. These compounds are a class of microbial secondary metabolites produced by various microorganisms, and they possess significant medical and biotechnological importance. The defining structural feature of these compounds is the presence of both a hydrophobic fragment, primarily a hydrocarbon tail of varying length, and a hydrophilic cyclic peptide moiety. This hydrocarbon tail confers amphiphilic properties to the lipopeptides, which are essential for their broad spectrum of biological activities. Their mechanism of action involves disruption of the cell membrane, and in many cases, the formation of ion-permeable defects has also been shown. Results: This review summarizes the data on cyclic lipopeptides produced by Pseudomonas spp., Streptomyces spp., and Bacillus spp. that modify membrane permeability through the formation of ion channels. The main emphasis is on understanding how the structure of the CLP can be related to the probability and mode of pore formation. Conclusions: The findings can contribute to expanding the arsenal of effective antimicrobial agents with a mechanism of action that reduces the risk of developing resistance.