Dialectics of antimicrobial peptides I: common mechanisms of offensive and protecting roles of the peptides

• DOI: 10.48550/arxiv.2502.09408
• Publication Date: 2025-02-13
• Authors: Marta V. Volovik; Z. G. Denieva; Oleg V. Kondrashov; Sergey A. Akimov; Oleg V. Batishchev
• Keywords: Offensive; Dialectic

Antimicrobial peptides (AMPs) have intrigued researchers for decades due to the contradiction between their high potential against resistant bacteria and inability find a structure-function relationship development of an effective non-toxic agent. In present study companion paper [Phys. Rev. E (2024)], we performed comprehensive experimental theoretical analysis various aspects AMP-membrane interactions AMP-induced pore formation. Using well-known melittin magainin as examples, showed, using patch-clamp fluorescence measurements, that these peptides, even at nanomolar concentrations, modify membrane by making it permeable protons (and, possibly, water), but not ions, protect from large formation after subsequent addition 20-fold higher concentrations AMPs. This protective effect is independent side (or both sides) peptide determined peptide-induced deformations membrane. Peptides create small, H+-permeable pores incessantly connect opposing leaflets, allowing translocation lipids thus preventing further generation lateral pressure/tension imbalance. At same time, such imbalance key AMP with main contribution coming single ion-conducting events rather than stable channel-like structures. Therefore, our results suggest lowering concentration, which common principle reduce toxicity, may actually make AMP. However, pre-treatment be eukaryotic cells