文献类型：期刊文献

英文题名：Correlating antimicrobial activity and model membrane leakage induced by nylon-3 polymers and detergents

作者：Hovakeemian, Sara G.[1];Liu, Runhui[2,3,4];Gellman, Samuel H.[2];Heerklotz, Heiko[1,5,6]

机构：[1]Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 1A1, Canada;[2]Univ Wisconsin, Dept Chem, Madison, WI 53706 USA;[3]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[5]Univ Freiburg, Inst Pharmaceut Sci, Freiburg, Germany;[6]BIOSS Ctr Biol Signalling Studies, Freiburg, Germany

年份：2015

卷号：11

期号：34

起止页码：6840

外文期刊名：SOFT MATTER

收录：;EI(收录号：20153401204122);WOS:【SCI-EXPANDED(收录号:WOS:000360070700012)】；

基金：Constructive comments on the manuscript by Sebastian Fiedler and Helen Y. Fan are gratefully acknowledged. This work was supported by a grant from the National Science and Engineering Council of Canada to H.H. and by NIH grant R01GM093265 to S.H.G.

语种：英文

外文关键词：Yeast - Rayon - Polyamides - Lipid bilayers - Microorganisms - Soaps (detergents)

摘要：Most antimicrobial peptides act upon target microorganisms by permeabilizing their membranes. The mode of action is often assessed by vesicle leakage experiments that use model membranes, with the assumption that biological activity correlates with the permeabilization of the lipid bilayer. The current work aims to extend the interpretation of vesicle leakage results and examine the correlation between vesicle leakage and antimicrobial activity. To this end, we used a lifetime-based leakage assay with calcein-loaded vesicles to study the membrane permeabilizing properties of a novel antifungal polymer poly-NM, two of its analogs, and a series of detergents. In conjunction, the biological activities of these compounds against Candida albicans were assessed and correlated with data from vesicle leakage. Poly-NM induces all-or-none leakage in polar yeast lipid vesicles at the polymer's MIC, 3 mu g mL(-1). At this and higher concentrations, complete leakage after an initial lag time was observed. Concerted activity tests imply that this polymer acts independently of the detergent octyl glucoside (OG) for both vesicle leakage and activity against C. albicans spheroplasts. In addition, poly-NM was found to have negligible activity against zwitterionic vesicles and red blood cells. Our results provide a consistent, detailed picture of the mode of action of poly-NM: this polymer induces membrane leakage by electrostatic lipid clustering. In contrast, poly-MM: CO, a nylon-3 polymer comprised of both cationic and hydrophobic segments, seems to act by a different mechanism that involves membrane asymmetry stress. Vesicle leakage for this polymer is transient (limited to <100%) and graded, non-specific among zwitterionic and polar yeast lipid vesicles, additive with detergent action, and correlates poorly with biological activity. Based on these results, we conclude that comprehensive leakage experiments can provide a detailed description of the mode of action of membrane permeabilizing compounds. Without this thorough approach, it would have been logical to assume that the two nylon-3 polymers we examined act via similar mechanisms; it is surprising that their mechanisms are so distinct. Some, but not all mechanisms of vesicle permeabilization allow for antimicrobial activity.