ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2024-2-55-64ssmu-5662Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSВосстановление антибиотикочувствительности к линкомицину в составе композиций с наносеребром и гуминовыми веществамиRestoring antibiotic sensitivity to lincomycin in compositions with nanosilver and humic substanceshttps://orcid.org/0000-0002-1973-8983ЗыковаМ. В.ZykovaM. V.

Зыкова Мария Владимировна – д-р фармацевт. наук, доцент, зав. кафедрой химии 

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

zykova.mv@ssmu.ruЧжанЮ.ZhangYun

Чжан Юй – аспирант, кафедра медицинской химии и тонкого органического синтеза, химический факультет 

119991, г. Москва, Ленинские Горы, 1-3

1-3, Leninskie Gory, Moscow, 119991

zhangyu13051837552@gmail.comhttps://orcid.org/0000-0002-8387-9780ЛысенкоИ. В.LysenkoI. V.

Лысенко Илья Владимирович – зам. проректора по образовательной деятельности 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

lussenkoilya@gmail.comАрутюнянД. А.ArutyunyanD. A.

Арутюнян Дмитрий Альбертович – студент, кафедра химической энзимологии, химический факультет 

119991, г. Москва, Ленинские Горы, 1-3

1-3, Leninskie Gory, Moscow, 119991

dmitrii.arutiunian@chemistry.msu.ruhttps://orcid.org/0000-0002-0167-7043АзаркинаЛ. А.AzarkinaL. A.

Азаркина Людмила Анатольевна – канд. фармацевт. наук, доцент кафедры химии 

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

ludmila_logvinova@mail.ruhttps://orcid.org/0000-0002-5292-1368МихалевД. А.MikhalevD. A.

Михалев Дмитрий Александрович – ассистент, кафедра химии 

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

diman021999@gmail.comhttps://orcid.org/0000-0002-2153-7945БелоусовМ. В.BelousovM. V.

Белоусов Михаил Валерьевич – д-р фармацевт. наук, профессор, зав. кафедрой фармацевтического анализа 

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

mvb63@mail.ruhttps://orcid.org/0000-0001-9084-7851ПерминоваИ. В.PerminovaI. V.

Перминова Ирина Васильевна – д-р хим. наук, профессор, зав. научно-исследовательской лабораторией природных гуминовых систем, кафедра медицинской химии и тонкого органического синтеза 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

iperminova@gmail.comСибирский государственный медицинский университет (СибГМУ)РоссияSiberian State Medical UniversityRussian FederationМосковский государственный университет (МГУ) им. М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian FederationЮжно-Уральский государственный медицинский университет (ЮУГМУ)РоссияSouth Ural State Medical UniversityRussian Federation2024100720242325564Copyright © Зыкова М.В., Чжан Ю., Лысенко И.В., Арутюнян Д.А., Азаркина Л.А., Михалев Д.А., Белоусов М.В., Перминова И.В., 20242024Зыкова М.В., Чжан Ю., Лысенко И.В., Арутюнян Д.А., Азаркина Л.А., Михалев Д.А., Белоусов М.В., Перминова И.В.Zykova M.V., Zhang Y., Lysenko I.V., Arutyunyan D.A., Azarkina L.A., Mikhalev D.A., Belousov M.V., Perminova I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5662

Цель – исследование восстановления чувствительности метициллин-резистентного штамма Staphylococcus aureus к линкомицину при добавлении гуминовых веществ с наночастицами серебра. Материалы и методы. Композиции гуминовых веществ с наночастицами серебра синтезировали из коммерческого гумата натрия Powhumus и нитрата серебра в присутствии NaOH (1 моль) для создания щелочной среды. Для синтеза одной из двух композиций гумат натрия модифицировали гидрохиноном. Для описания характеристик полученных составов снимали спектры поверхностного плазмонного резонанса наночастиц серебра и их изображения, полученные методом просвечивающей электронной микроскопии. Чувствительность клинического штамма Staphylococcus aureus, устойчивого к метициллину, определяли, измеряя минимальную ингибирующую концентрацию (МИК), с введением в состав композиций линкомицина и тетрациклина. Результаты. Показана 100%-я конверсия ионного серебра в металлическое с характерным размером наночастиц 6 нм. Проведено сравнение действия тетрациклина и линкомицина на исследуемый штамм S. aureus, показаны высокая чувствительность к тетрациклину (МИК < 10 мкг/мл) и отсутствие чувствительности к линкомицину (МИК > 200 мкг/мл). Исследование действия композиции гуматов натрия с наносеребром при введении в них линкомицина показало, что подобный подход позволяет существенно снизить МИК линкомицина до 0,1 мкг/мл в присутствии композиций с модифицированным гидрохиноном гумата натрия в концентрации 40 мкг/мл и композиций с немодифицированным гуматом натрия в концентрации 60 мкг/ мл. Заключение. В проведенном исследовании продемонстрировано, что при использовании композиций гуминовых веществ с наносеребром происходит полное восстановление чувствительности к линкомицину устойчивого к метициллину штамма Staphylococcus aureus. 

Aim. To study the effect of compositions with nanosilver and humic substances on restoration of sensitivity of methicillin-resistant Staphylococcus aureus to lincomycin. Materials and methods. Compositions of humic substances with silver nanoparticles were synthesized from commercial sodium humate Powhumus and silver nitrate in the presence of NaOH (1 M) to modulate alkaline pH. To synthesize one of the two compositions, sodium humate was modified with hydroquinone. To describe the characteristics of the resulting compositions, surface plasmon resonance spectra of silver nanoparticles and their images obtained by transmission electron microscopy were recorded. Sensitivity of a clinical strain of methicillinresistant Staphylococcus aureus was determined by measuring the minimum inhibitory concentration (MIC) with the addition of lincomycin and tetracycline to the compositions. Results. 100% conversion of ionic silver into metallic silver with a characteristic nanoparticle size of 6 nm was shown. The effects of tetracycline and lincomycin on the studied strain of Staphylococcus aureus were compared, and high sensitivity to tetracycline (MIC < 10 μg / ml) and resistance to lincomycin (MIC > 200 μg / ml) were shown. Studying the effect of the composition containing sodium humates with nanosilver with the introduction of lincomycin into it showed that this approach can significantly reduce MIC of lincomycin to 0.1 μg/ml in the presence of compositions with hydroquinone-modified sodium humate at a concentration of 40 μg / ml and compositions with unmodified sodium humate at a concentration of 60 μg / ml. Conclusion. The study demonstrated that the use of compositions with humic substances and nanosilver completely restores sensitivity of methicillin-resistant Staphylococcus aureus to lincomycin.

наночастицы серебрагуминовые веществалинкомицинсинергетический эффектантибиотикорезистентностьStaphylococcus aureussilver nanoparticleshumic substanceslincomycinsynergistic effectantibiotic resistanceStaphylococcus aureusРабота выполнена при финансовой поддержке гранта РНФ № 20-63-47070 (синтез композиций наносеребра с гуминовыми веществами и комбинированных препаратов с антибиотиками) и гранта РНФ 20-65-47052 (определение антимикробной активности). Исследование наночастиц было выполнено в Центре коллективного пользования «Нанохимия и наноматериалы» на оборудовании (просвечивающим микроскопе), приобретенном на средства программы МГУ «Развитие».The work was carried out with the financial support of the Russian Science Foundation Grant No. 20-63-47070 (synthesis of compositions with nanosilver and humic substances and combination drugs with antibiotics) and the Russian Science Foundation Grant No. 20-65-47052 (determination of antimicrobial activity). 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The authors declare that there are no conflicts of interest present.