The Membrane-Water Partition Coefficients of Antifungal, but Not Antibacterial, Membrane-Active Compounds Are Similar.

Pavel E Volynsky,Fedor F Severin,Svyatoslav S Sokolov,Sergey A Akimov,Alexandra I Smirnova

doi:10.3389/fmicb.2021.756408

Abstract

The Membrane-Water Partition Coefficients of Antifungal, but Not Antibacterial, Membrane-Active Compounds Are Similar.

Highlights

Sterols are essential components of eukaryotic membranes and play a structural role, increasing the resistance of the phospholipid bilayer to various stresses (Evans and Rawicz, 1990; Zhelev and Needham, 1993; Michalak et al, 2013; Hannesschlaeger et al, 2019)
The clustering of the compounds with antifungal activity obviously suggests a common mechanism of their action
Rather than puncturing the plasma membrane, these compounds seem to induce intracellular changes: inhibit the hyphal growth and/or biofilm formation, cause ROS generation, etc. This is consistent with the protective role of ergosterol against pore formation (Figure 1A)

Summary

INTRODUCTION

Sterols are essential components of eukaryotic membranes and play a structural role, increasing the resistance of the phospholipid bilayer to various stresses (Evans and Rawicz, 1990; Zhelev and Needham, 1993; Michalak et al, 2013; Hannesschlaeger et al, 2019). A drug-membrane interaction can be divided into two stages: first, a drug moves from the aqueous phase into the water-membrane interface saturated by polar and charged groups. It penetrates into the hydrophobic core of the phospholipid bilayer. We have deliberately limited our analysis to such practically used compounds because their biological activities are, obviously, characterized more thoroughly than the ones of the chemicals used, for instance, for research purposes only It appeared that while antibacterial compounds differed considerably in terms of the energy costs, antifungal compounds displayed a significant degree of similarity. This finding suggests a common mechanism for the interaction between the antifungal membrane-active compounds and the fungal plasma membrane

Sterols Stabilize Membranes by Preventing Pore Formation

DISCUSSION