mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2021.024mes-147Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕORIGINAL RESEARCHВзаимодействие катионных антисептиков с кардиолипинсодержащей модельной бактериальной мембранойInteraction of cationic antiseptics with cardiolipin-containing model bacterial membranesХолинаЕ. Г.KholinaE. G.

ул. Ореховый бульвар, д. 28, 115682, г. Москва

Orekhovyi bulvar, 28, Moscow, 115682

БоздаганянМ. Е.BozdaganyanM. E.

ул. Ореховый бульвар, д. 28, 115682, г. Москва

Orekhovyi bulvar, 28, Moscow, 115682

СтраховскаяМ. Г.StrakhovskayaM. G.

ул. Ореховый бульвар, д. 28, 115682, г. Москва

Orekhovyi bulvar, 28, Moscow, 115682

КоваленкоИ. Б.KovalenkoI. B.

Илья Борисович Коваленко

ул. Ореховый бульвар, д. 28, 115682, г. Москва

Ilya B. Kovalenko

Orekhovyi bulvar, 28, Moscow, 115682

ikovalenko78@gmail.comФедеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства; Московский государственный университет имени М. В. ЛомоносоваРоссияFederal Scientific and Clinical Center of Specialized Medical Care and Medical Technology of FMBA; Lomonosov Moscow State UniversityRussian Federation2021261020242333845Copyright © Холина Е.Г., Боздаганян М.Е., Страховская М.Г., Коваленко И.Б., 20242024Холина Е.Г., Боздаганян М.Е., Страховская М.Г., Коваленко И.Б.Kholina E.G., Bozdaganyan M.E., Strakhovskaya M.G., Kovalenko I.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/147

Плазматическая мембрана является одной из главных мишеней действия катионных антисептиков (КА). Целью исследования было изучить на молекулярном уровне действие относящихся к разным химическим классам КА на кардиолипинсодержащие участки плазматической бактериальной мембраны. Исследование выполнено с применением крупнозернистого молекулярного моделирования. На основе созданных крупнозернистых молекулярных моделей КА, включая мирамистин, хлоргексидин, пиклоксидин и октенидин, изучено их взаимодействие с липидным кардиолипинсодержащим бислоем. КА снижали коэффициенты латеральной диффузии липидов и увеличивали площадь поверхности мембраны, приходящуюся на липид. Кроме мирамистина, все КА снижали параметры порядка жирнокислотных цепей липидов. Добавление октенидина в соотношении КА : липид как 1 : 4 приводило к кластеризации кардиолипина с последующим вырыванием из модельного бислоя нейтральных молекул фосфатилилэтаноламина. Выявлено, что КА обладают способностью сорбироваться на липидном бислое, вызывая кластеризацию отрицательно заряженных липидов. Антисептик октенидин вызывает образование кардиолипиновых микродоменов. Нарушение латерального распределения липидов и вырывание молекул фосфатидилэтаноламина может привести к повышению проницаемости липидного бислоя. 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.

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.

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The authors declare that there are no conflicts of interest present.