1+1=3? Concerted Action of Membrane Permeabilizers

Abstract

Certain antibiotic peptides are thought to permeabilize membranes of pathogens by effects that are also observed for simple detergents, such as membrane thinning and disordering, asymmetric bilayer expansion, toroidal pore formation, and micellization. Here we test the hypothesis that such peptides act additively with detergents when applied in parallel. Additivity is defined analogously to a fractional inhibitory concentration index (FICI) of unity, and the extent and mechanism of leakage are measured by the fluorescence lifetime-based vesicle leakage assay using calcein-loaded vesicles. Concerted action was tested for the detergent C12EO8 with the detergents octyl glucoside and CHAPS, the antimicrobial peptide magainin 2, and the fungicidal lipopeptides surfactin, fengycin and iturin from Bacillus subtilis QST713, respectively. The results are discussed in terms of an optimum heterogeneity of the system that governs the leakage mechanism, extent of leakage, and additivity of action with another agent. The results are important for understanding the nature of detergent-like actions of peptides as well as for optimizing formulations of such antimicrobials for medical applications or crop protection.