danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2026-70-1-32-44dan-1292Research ArticleХИМИЯCHEMISTRYФосфатидацилгидролаза как фактор вирулентности условно-патогенных микроорганизмов в реакциях гидролиза липоконъюгатовPhosphatidacylhydrolase as a virulence factor of opportunistic microorganisms in lipoconjugate hydrolysis reactionsЛитвинкоН. М.LitvinkoN. M.

Литвинко Наталья Михайловна – д-р хим. наук, профессор, заведующий лабораторией.

Ул. Купревича, 5/2, 220084, Минск

Litvinko Natalia M. – D. Sc. (Chemistry), Professor, Head of the Laboratory.

5/2, Kuprevich Str., 220084, Minsk

al_h@mail.ruГерловскийД. О.GerlovskyD. O.

Герловский Денис Олегович – канд. хим. наук, доцент, научный сотрудник.

Ул. Купревича, 5/2, 220084, Минск

Gerlovsky Denis O. – Ph. D. (Chemistry), Assistant Professor, Researcher.

5/2, Kuprevich Str., 220084, Minsk

denis2904-83@mail.ruМихайлопулоИ. А.MikhailopuloI. A.

Михайлопуло Игорь Александрович – член-корреспондент, д-р хим. наук, гл. науч. сотрудник.

Ул. Купревича, 5/2, 220084, Минск

Mikhailopulo Igor A. – Corresponding Member, D. Sc. (Chemistry), Chief Researcher.

5/2, Kuprevich Str., 220084, Minsk

imikhailopulo@gmail.comИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus2026020320267013244Copyright © Литвинко Н.М., Герловский Д.О., Михайлопуло И.А., 20262026Литвинко Н.М., Герловский Д.О., Михайлопуло И.А.Litvinko N.M., Gerlovsky D.O., Mikhailopulo I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/1292

Впервые в качестве субстратов фосфатидацилгидролазы (фосфолипазы типа А) в реакциях фосфолиполиза исследованы фосфатидильные производные ряда нуклеозидов. Предложен и изучен новый пусковой механизм, инициирующий гибель патогенных и условно-патогенных микроорганизмов (клеток Staphylococcus aureus и Candida spp.), за счет их вирулентности, обеспечиваемой в том числе активностью собственных фосфолипаз типа А, под действием лекарственных форм антибиотиков (на основе ковалентно и нековалентно модифицированных липоконъюгатов) пуринового (неларабин, азотистое основание гуанин) и пиримидинового (бривудин, азотистое основание урацил) ряда, обладающих бактерицидным действием. В части устойчивости новых лекарственных форм к деструкции в пищеварительном тракте показано, что липоконъюгат бривудина наиболее подвержен гидролизу с участием панкреатической фосфолипазы А2, а липоконъюгат на основе неларабина отличается более высокой стабильностью к фосфолиполизу. Установлено, что поскольку скорость гидролиза липоконъюгатов неларабина и бривудина фосфолипазой А культуральной жидкости Candida sake и Staphylococcus aureus соответственно в 1,7 и 2 раза выше, чем фосфатидилхолина, они могут служить основой для создания биоцидсодержащих наноконтейнеров и облегчать за счет повышенной гидролизуемости доступность действующего вещества.

For the first time, phosphatidyl derivatives of a number of nucleosides were studied as substrates of phosphatidylacylhydrolase in phospholipolysis reactions. A new trigger mechanism has been proposed and studied that initiates the death of pathogenic and opportunistic microorganisms (Staphylococcus aureus and Candida spp. cells) due to their virulence, including the activity of their own type A phospholipases, under the action of medicinal forms of antibiotics (based on covalently and non-covalently modified lipoconjugates) of the purine (nelarabine, nitrogenous base guanine) and pyrimidine (brivudine, nitrogenous base uracil) series, which have a bactericidal effect. In terms of the resistance of forms to destruction in the digestive tract, it has been shown that brivudine lipoconjugates are most susceptible to hydrolysis with the participation of pancreatic phospholipase A2, while nelarabine-based lipoconjugate is characterized by higher stability to phospholipolysis. It has been established that, since the rate of hydrolysis of lipoconjugates of nelarabine and brivudine by phospholipase A of the culture fluid of Candida sake and Staphylococcus aureus is 1.7 and 2 times higher, respectively, than that of phosphatidylcholine, they can serve as a basis for the demonstration of biocide-containing conjugates and facilitate the availability of the active substance due to increased hydrolyzability.

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