microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2021-4-46-53microbe-1590Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМоделирование экспериментальной чумы в условиях лаборатории уровня биобезопасности 2.Simulation of Bubonic Plague in BSL-2 Laboratoryhttps://orcid.org/0000-0001-7280-3660ВагайскаяА. С.VagaiskayaA. S.

Российская Федерация, 142279, Московская обл., р.п. Оболенск

Obolensk, Moscow Region, 142279, Russian Federation

Vagaiskaia@obolensk.orghttps://orcid.org/0000-0001-9223-2105ТруняковаА. С.TrunyakovaA. S.

Российская Федерация, 142279, Московская обл., р.п. Оболенск

Obolensk, Moscow Region, 142279, Russian Federation

https://orcid.org/0000-0003-1959-1739КомбароваТ. И.KombarovaT. I.

Российская Федерация, 142279, Московская обл., р.п. Оболенск

Obolensk, Moscow Region, 142279, Russian Federation

https://orcid.org/0000-0002-1996-8949ДентовскаяС. В.DentovskayaS. V.

Российская Федерация, 142279, Московская обл., р.п. Оболенск

Obolensk, Moscow Region, 142279, Russian Federation

ФБУН «Государственный научный центр прикладной микробиологии и биотехнологии»РоссияState Research Center for Applied Microbiology and BiotechnologyRussian Federation202125012022044653Copyright © Вагайская А.С., Трунякова А.С., Комбарова Т.И., Дентовская С.В., 20222022Вагайская А.С., Трунякова А.С., Комбарова Т.И., Дентовская С.В.Vagaiskaya A.S., Trunyakova A.S., Kombarova T.I., Dentovskaya S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.microbe.ru/jour/article/view/1590

Возбудитель чумы, Yersinia pestis, относится к I группе патогенности (опасности), что подразумевает работу с его штаммами «дикого типа» в УББ 3 (уровень биобезопасности) лаборатории. Y. pestis EV НИИЭГ является Δpgm штаммом, что позволяет проводить эксперименты в УББ 2 лаборатории. Однако возникновение и развитие заболевания, вызванное этим штаммом, не может полностью повторять наблюдаемое при использовании вирулентных аналогов. Остаточную вирулентность штамма Y. pestis EV НИИЭГ для мышей можно повысить при введении препаратов железа in vivo. Цель исследования состояла в оптимизации методических приемов моделирования экспериментальной чумы у лабораторных животных после введения аттенуированных Δpgm штаммов Y. pestis с использованием декстрана железа. Материалы и методы. Моделирование чумной инфекции у беспородных мышей проводили путем подкожного введения штамма Y. pestis EV НИИЭГ с добавлением декстрана железа. У животных ежедневно проводили оценку здоровья. В ходе эксперимента оценивали патологоанатомическую картину и обсемененность органов у мышей. Результаты и обсуждение. При подкожном введении штамма Y. pestis EV НИИЭГ в присутствии декстрана железа у мышей наблюдали бубонную форму чумы, приводящую к летальному исходу с патологическими изменениями внутренних органов, характерными для чумной инфекции. При ежедневном введении железа LD50 штамма Y. pestis EV НИИЭГ для мышей достоверно превышала таковую при однократном введении препарата. Различия в выживаемости животных в группах с однократным и многократным введением железа по сравнению с контрольными группами были достоверны. Таким образом, аттенуированные Δpgm штаммы Y. pestis в присутствии декстрана железа могут быть использованы в условиях лаборатории УББ 2 для воспроизведения экспериментальной чумы у мышей с выраженными патологоанатомическими изменениями и летальностью.

The causative agent of plague, Yersinia pestis, is classified as pathogenicity (hazard) group I agent, which means that the work with “wild type” strains should be carried out in BSL-3 facilities. Y. pestis EV NIIEG is a Δpgm strain, allowing experimental studies to be carried out in BSL-2 laboratories. However, the disease and its progression elicited by such strain do not entirely mirror the infection observed with fully virulent strains. Residual virulence of Y. pestis EV NIIEG strain for mice can be increased under in vivo iron supplementation. The aim of the study was to optimize methodological approaches to modeling experimental plague in laboratory animals following administration of attenuated Δpgm Y. pestis strains with iron dextran. Materials and methods. Simulation of plague infection in outbred mice was carried out through subcutaneous inoculation of Y. pestis EV NIIEG strain with iron dextran supplementation. The animal condition was assessed on a daily basis. In the course of the experiment, the pathological presentation and bacterial content in organs of mice were evaluated. Results and discussion. Mice inoculated subcutaneously with Y. pestis EV NIIEG strain in the presence of iron dextran developed a bubonic plague that resulted in lethal outcome with pathological changes of internal organs, characteristic of plague infection. In case of daily administration of iron, LD50 of Y. pestis EV NNIEG strain for the mice significantly exceeded the same one with a single injection. Differences in the survival rate among animals in the groups with a single and multiple administration of iron compared to the control group were statistically valid. Thus, attenuated Δpgm Y. pestis strains in the presence of iron dextran can be used to model experimental plague in mice with marked pathological changes and lethality in BSL-2 laboratories.

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