Взаимодействие катионных антисептиков с кардиолипинсодержащей модельной бактериальной мембраной

Eg Kholina,Me Bozdaganyan,Mg Strakhovskaya,Ib Kovalenko

doi:10.47183/mes.2021.024

Eg Kholina, Me Bozdaganyan + Show 2 more

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https://doi.org/10.47183/mes.2021.024

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Abstract

Plasma membrane is one of the major targets for cationic antiseptics (CA). The study was aimed to assess molecular effects of CAs of different chemical classes on cardiolipin-containing regions of bacterial plasma membranes. The study was carried out using coarse-grained molecular modeling. Interaction of CAs, such as miramistin, chlorhexidine, picloxidine, and octenidine, with cardiolipin-containing bilayer was assessed based on the CA coarse-grained models. CAs reduced lipid lateral diffusion coefficients and increased the membrane area per lipid. All CAs, except miramistin, reduced the lipid fatty acid chain order parameters. Adding octenidine at a CA : lipid ratio of 1 : 4 resulted in cardiolipin clustering with subsequent pulling the neutral phosphatidylethanolamine molecules out of the model bilayer. It was found that CАs have the potential for sorption to lipid bilayer, causing clustering of negatively charged lipids. Antiseptic octenidine causes formation of cardiolipin microdomains. Abnormal lateral lipid distribution together with pulling out phosphatidylethanolamine molecules can result in increased lipid bilayer permeability. The most significant reduction of cardiolipin lateral diffusion coefficient by 2.8 ± 0.4 times was observed in the presence of CA chlorhexidine at an antiseptic : lipid ratio of 1 : 4.

Highlights

Plasma membrane is one of the major targets for cationic antiseptics (CA)
Lipid mobility is a measure of how these biomolecules can move along the plane of bilayer, it is assessed based on lateral diffusion coefficients [26], which could be obtained from the molecular dynamics results [27]
Interaction of CAs belonging to biguanides (CHL, PIC) and quaternary ammonium compounds (QACs) (MIR, OCT) with the CL-containing model bilayer, simulating the plasma membrane at the cell poles of bacilliform bacteria, was studied based on the constructed coarse-grain models of these substances

Summary

Introduction

Plasma membrane is one of the major targets for cationic antiseptics (CA). The study was aimed to assess molecular effects of CAs of different chemical classes on cardiolipin-containing regions of bacterial plasma membranes. Interaction of CAs, such as miramistin, chlorhexidine, picloxidine, and octenidine, with cardiolipin-containing bilayer was assessed based on the CA coarse-grained models. Adding octenidine at a CA : lipid ratio of 1 : 4 resulted in cardiolipin clustering with subsequent pulling the neutral phosphatidylethanolamine molecules out of the model bilayer. КА снижали коэффициенты латеральной диффузии липидов и увеличивали площадь поверхности мембраны, приходящуюся на липид. Наиболее значимое уменьшение коэффициента латеральной диффузии липида кардиолипина в 2,8 ± 0,4 раза отмечено в присутствии КА хлоргексидина при соотношении антисептик : липид как 1 : 4. Г. Холина — создание молекулярных моделей исследуемых веществ, проведение расчетов, написание текста статьи; М. Е. Боздаганян — проведение расчетов, написание текста статьи; М. Г. Страховская — идея исследования, написание текста статьи, анализ результатов; И. Б. Коваленко — идея исследования, создание вычислительной инфраструктуры, написание текста статьи, анализ результатов

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