microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2024-4-42-53microbe-2078Research ArticleОБЗОРЫREVIEWSХолерные бактериофаги: история открытия, строение и применениеCholera Bacteriophages: History of Discovery, Structure and Applicationhttps://orcid.org/0000-0001-5759-3765ЧелдышоваН. Б.CheldyshovaN. B.

Челдышова Надежда Борисовна

410005, Саратов, ул. Университетская, 46

Nadezhda B. Cheldyshova

46, Universitetskaya St., Saratov, 410005

rusrapi@microbe.ruhttps://orcid.org/0000-0003-4366-0562ЗадноваС. П.ZadnovaS. P.

410005, Саратов, ул. Университетская, 46

46, Universitetskaya St., Saratov, 410005

https://orcid.org/0000-0002-8798-1547АбрамоваЕ. Г.AbramovaE. G.

410005, Саратов, ул. Университетская, 46

46, Universitetskaya St., Saratov, 410005

https://orcid.org/0000-0002-1130-3504НикифоровА. К.NikiforovA. K.

410005, Саратов, ул. Университетская, 46

46, Universitetskaya St., Saratov, 410005

https://orcid.org/0009-0005-8528-1933ДевдарианиЗ. Л.DevdarianiZ. L.

410005, Саратов, ул. Университетская, 46

46, Universitetskaya St., Saratov, 410005

ФКУН «Российский научно-исследовательский противочумный институт «Микроб»РоссияRussian Research Anti-Plague Institute “Microbe”Russian Federation202418122024044253Copyright © Челдышова Н.Б., Заднова С.П., Абрамова Е.Г., Никифоров А.К., Девдариани З.Л., 20242024Челдышова Н.Б., Заднова С.П., Абрамова Е.Г., Никифоров А.К., Девдариани З.Л.Cheldyshova N.B., Zadnova S.P., Abramova E.G., Nikiforov A.K., Devdariani Z.L.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/2078

Вирусы, поражающие холерный вибрион, или холерные бактериофаги, открыты в начале ХХ в., когда в Юго-Восточной Азии, на Дальнем и Ближнем Востоке и в Европе свирепствовала шестая пандемия холеры. Это открытие положило начало интенсивному изучению холерных бактериофагов как перспективного средства в борьбе с холерой. В обзоре освещены вопросы, связанные с историей открытия и изучения холерных бактериофагов, описаны особенности их строения и жизненного цикла. Представлена коэволюционная стратегия взаимодействия холерных бактериофагов с клетками холерного вибриона, получившая название «динамика Красной королевы». Согласно этой стратегии штаммы холерного вибриона и холерные бактериофаги для того, чтобы выжить, должны постоянно эволюционировать и приспосабливаться, приобретая всё новые системы защиты друг от друга. Также в обзоре изложены сведения об основных известных на сегодняшний день антифаговых системах холерного вибриона (мутационные изменения рецепторного аппарата, выброс везикул внешней мембраны, система рестрикции-модификации, PLE-элемент, SXT-элементы, система исключения бактериофага BREX и CRISPR/ Cas-системы, Abi-стратегия). Описаны фаговые системы контрзащиты (CRISPR/Cas-система, нуклеаза Odn, эпигенетическая модификация метилазой, система противодействия BREX). Проанализированы вопросы практического применения холерных бактериофагов в диагностике холеры (для идентификации, определения биовара возбудителя, его вирулентности и эпидемической значимости), приведены наиболее известные схемы фаготипирования. Охарактеризованы перспективные стратегии использования холерных бактериофагов в фаготерапии и фагопрофилактике холеры. Отдельно рассмотрены эффекты совместного использования фагов и антибиотиков в комплексной терапии.

Viruses that affect cholera vibrio, or cholera bacteriophages, were discovered in early twentieth century, when the sixth cholera pandemic was raging in Southeast Asia, the Far and Middle East and Europe. This discovery marked the beginning of intensive study of cholera bacteriophages as a promising means in the fight against cholera. The review highlights issues related to the history of the discovery and study of cholera bacteriophages and describes the features of their structure and life cycle. A co-evolutionary strategy for the interaction of cholera bacteriophages with Vibrio cholerae cells, called the “Red Queen dynamics”, is presented. According to this strategy, strains of V. cholerae and cholera bacteriophages, in order to survive, must constantly evolve and adapt, acquiring more and more new systems for defense from each other. The review also provides information about the main currently known anti-phage systems of V. cholerae (mutational changes in the receptor apparatus, release of outer membrane vesicles, restriction-modification system, PLE element, SXT elements, BREX bacteriophage exclusion system and CRISPR/Cas systems, Abi-strategy). Phage counter-defense systems are presented (CRISPR/Cas system, Odn nuclease, epigenetic modification by methylase, BREX countermeasures system). The papaer analyzes the practical application of cholera bacteriophages in the diagnosis of cholera (for identification, determination of the biovar of the pathogen, its virulence and epidemic significance), and outlines the most well-known phage typing schemes. Promising strategies for the use of cholera bacteriophages in phage therapy and phage prevention of cholera are characterized. The effects of combined use of phages and antibiotics in complex therapy are considered separately.

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