The Bacteriostatic Activity of 2-Phenylethanol Derivatives Correlates with Membrane Binding Affinity.

Isabel S Kleinwächter,Eckhard Thines,Dirk Schneider,Nadja Hellmann,Alessia Centi,Stefanie Pannwitt,Tristan Bereau

doi:10.3390/membranes11040254

Abstract

The hydrophobic tails of aliphatic primary alcohols do insert into the hydrophobic core of a lipid bilayer. Thereby, they disrupt hydrophobic interactions between the lipid molecules, resulting in a decreased lipid order, i.e., an increased membrane fluidity. While aromatic alcohols, such as 2-phenylethanol, also insert into lipid bilayers and disturb the membrane organization, the impact of aromatic alcohols on the structure of biological membranes, as well as the potential physiological implication of membrane incorporation has only been studied to a limited extent. Although diverse targets are discussed to be causing the bacteriostatic and bactericidal activity of 2-phenylethanol, it is clear that 2-phenylethanol severely affects the structure of biomembranes, which has been linked to its bacteriostatic activity. Yet, in fungi some 2-phenylethanol derivatives are also produced, some of which appear to also have bacteriostatic activities. We showed that the 2-phenylethanol derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate, but not Tyrosol, were fully incorporated into model membranes and affected the membrane organization. Furthermore, we observed that the propensity of the herein-analyzed molecules to partition into biomembranes positively correlated with their respective bacteriostatic activity, which clearly linked the bacteriotoxic activity of the substances to biomembranes.

Highlights

Due to their amphipathic properties, alcohols affect numerous biological processes, many of which are related to cellular membranes
The impact of alcohols on biomembranes has been studied to a great extent using, aliphatic primary alcohols, albeit aromatic alcohols, such as 2-phenylethanol (2-PEtOH), insert into lipid bilayers and disturb the membrane organization [4]
We showed that the 2-PEtOH derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate (Figure 1) were incorporated into the model membranes and affected the membrane structure

Summary

Introduction

Due to their amphipathic properties, alcohols affect numerous biological processes, many of which are related to cellular membranes. As observed with other alcohols, the interaction of 2-PEtOH with the model as well as with biological membranes results in a drastic change of the lipid acyl-chain order [14,15,16]. Fungi produce some 2-PEtOH-derivatives, such as Tyrosol, phenyllactic acid, and phenylacetic acid (Figure 1), some of which appear to have bacteriostatic activities. Just as for 2-PEtOH, for phenyllactic acid, diverse modes of actions are discussed, and the compound appears to affect the integrity of the bacterial cell wall [14,20], and/or it might intercalate into the DNA and hinder DNA replication [23]. We showed that the 2-PEtOH derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate (Figure 1) were incorporated into the model membranes and affected the membrane structure. We observed a positive correlation between membrane partitioning and the bacteriostaticity of the here analyzed 2-PEtOH derivatives

Lipids and Chemicals

Computer Simulations

Results and Discussion