Abstract

Lantibiotics are a class of polycyclic peptide antibiotics known for their potent antimicrobial activity, which is often mediated by their ability to form pores or channels in bacterial cell membranes. The precise mechanism and efficiency of this channel formation are critically dependent on the physicochemical properties of the target membrane. This study investigates the **dependence of the channel-forming ability of lantibiotics on the lipid composition of the membranes**, a key factor governing their biological efficacy. Using model liposomes of varying lipid compositions, including zwitterionic and anionic phospholipids, we employed electrophysiological techniques and fluorescence spectroscopy to quantify the membrane-disrupting activity of a representative lantibiotic. Our results demonstrate a significant enhancement of channel formation in membranes containing a higher proportion of anionic lipids, suggesting a strong electrostatic interaction between the positively charged lantibiotic and the negatively charged lipid headgroups. Furthermore, the presence of specific lipids, such as cholesterol, was found to modulate channel stability and lifetime. These findings provide crucial insights into the molecular determinants of lantibiotic action, which can inform the rational design of new, more effective antimicrobial agents with tailored membrane specificity.