vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-936Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEРоль вторичного окислительного стресса в бактерицидном действии антибиотиковRole of secondary oxidative stress in the bactericidal action of antibioticshttps://orcid.org/0000-0002-3477-750XАховаА. В.AkhovaA. V.

Ахова Анна Викторовна – канд. биол. наук, науч. сотр. лаборатории адаптации микроорганизмов ИЭГМ УрО РАН 

614081, г. Пермь, ул. Голева, д. 13

Тел.: 8-342-212-2159

akhovan@mail.ruhttps://orcid.org/0000-0002-8631-8583ТкаченкоА. Г.TkachenkoA. G.

Ткаченко Александр Георгиевич – докт. мед. наук, зав. лабораторией адаптации микроорганизмов ИЭГМ УрО РАН 

614081, г. Пермь, ул. Голева, д. 13

Тел.: 8-342-212-2159

Институт экологии и генетики микроорганизмов, Пермский федеральный исследовательский центр, УрО РАНРоссияInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of SciencesRussian Federation202006112020754258264Copyright © Ахова А.В., Ткаченко А.Г., 20202020Ахова А.В., Ткаченко А.Г.Akhova A.V., Tkachenko A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/936

Воздействие β-лактамных, фторхинолоновых и аминогликозидных антибиотиков вызывало усиление продукции пероксида водорода и активацию экспрессии генов защиты от окислительного стресса (OxyR-регулон) по принципу доза-эффект в клетках Escherichia coli. В условиях микроаэрации ослабление интенсивности вторичного окислительного стресса, вызванного воздействием антибиотика, за счет добавки антиоксиданта тиомочевины оказывало влияние на антибактериальную активность фторхинолонов. Добавка антиоксиданта потенцировала сублетальное (не вызывавшее снижение количества колониеобразующих единиц ниже уровня 103/мл) действие антибиотика и повышала выживаемость бактериальных клеток, подвергнутых действию летальных доз. В присутствии антиоксиданта экспрессия генов OxyR-регулона, активированная сублетальным воздействием антибиотика, снижалась до уровня нестрессированной культуры. В условиях воздействия летальных доз антибиотика при добавке тиомочевины также наблюдалось снижение экспрессии генов антиоксидантной защиты, однако повышенный по сравнению с контролем уровень экспрессии сохранялся. Это может свидетельствовать о двойственной роли активных форм кислорода в условиях воздействия антибиотиков как повреждающих агентов, вносящих вклад в гибель клеток, и как сигнальных молекул, активирующих защитные механизмы.

Exposure to β-lactam, fluoroquinolone and aminoglycoside antibiotics caused an increase in the production of hydrogen peroxide and the expression of OxyR-regulon of the oxidative stress response in Escherichia coli cells. Under the conditions of microaeration, the attenuation of secondary oxidative stress due to the addition of an antioxidant thiourea affected the antibacterial effect of fluoroquinolones. Thiourea potentiated the effect of sub-lethal (which did not reduce the number of colony-forming units below 103/mL) doses of the antibiotic and increased the viability of cells exposed to lethal doses. The addition of thiourea reduced the expression of OxyR-regulon, increased by the sub-lethal antibiotic action, to an antibiotic-free culture level. When exposed to lethal doses, a decrease in the antibiotic-mediated expression of oxidative stress response genes in the presence of thiourea was also observed, however, the expression level remained higher as compared to an antibiotic-free culture. This may indicate the dual role of ROS under antibiotic treatment as the damaging agents contributing to killing and the signal molecules activating stress responses.

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