Water-membrane partition and the mutant selection window of antimicrobial peptides: insights from liposome studies.

Autor: Carneri F; Department of Chemical Science and Technologies, Tor Vergata University of Rome, 00133 Rome, Italy; Photoinduced Processes and Technologies Doctoral School, Department of Chemistry, Biology and Biotechnology, Perugia University, 06123 Perugia, Italy., Troiano C; Department of Chemical Science and Technologies, Tor Vergata University of Rome, 00133 Rome, Italy., Giaquinto G; Department of Chemical Science and Technologies, Tor Vergata University of Rome, 00133 Rome, Italy., Roversi D; Department of Chemical Science and Technologies, Tor Vergata University of Rome, 00133 Rome, Italy., Franzyk H; Department of Drug Design and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark., Stella L; Department of Chemical Science and Technologies, Tor Vergata University of Rome, 00133 Rome, Italy. Electronic address: stella@stc.uniroma2.it.
Jazyk: angličtina
Zdroj: Journal of colloid and interface science [J Colloid Interface Sci] 2024 Dec 19; Vol. 683 (Pt 1), pp. 1078-1086. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1016/j.jcis.2024.12.099
Abstrakt: The mutant selection window (MSW) is a range of antimicrobial concentrations, where some bacteria are killed, while others survive. Within this interval resistance may develop. Antimicrobial peptides (AMPs) are a promising class of antimicrobials that generally act by perturbing the integrity of bacterial membranes. Their MSW is typically narrower than that of traditional antibiotics, but it still encompasses about one order of magnitude of peptide concentrations. Phenotypic or genetic differences between individual cells may cause this heterogeneous bacterial response to AMPs. Therefore, we minimized the system complexity by investigating pore formation in liposomes with homogeneous size and composition. Surprisingly, the AMPs novicidin, P9-4, and Sub3 formed pores only in a fraction of vesicles, over a wide range of total peptide concentrations. By characterizing the water/membrane partition equilibrium of these three AMPs, we were able to report the vesicle-perturbing activity as a function of the membrane-bound peptide concentration. In this case, the curves became essentially step functions with well-defined (bound) concentration thresholds at which pores were formed in all liposomes. Therefore, the apparent heterogeneous effects of AMPs on vesicles were actually determined by variations in the fraction of membrane-bound peptides under different conditions, due to water-membrane partition. Unexpectedly, the thresholds coincided for all peptides in terms of bound amino acids per lipid (∼0.4), suggesting that the mechanism of pore formation primarily depends on the surface coverage by the AMPs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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