Молекулярные механизмы персистенции бактерий

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Журнал микробиологии, эпидемиологии и иммунобиологии. 2020; 97: 271-279

Молекулярные механизмы персистенции бактерий

Андрюков Борис Георгиевич, Ляпун Ирина Николаевна

https://doi.org/10.36233/0372-9311-2020-97-3-10

Аннотация

Высокий уровень смертности от инфекционных болезней в значительной степени опосредован повсеместным и бесконтрольным использованием антибиотиков, что привело к появлению лекарственно-резистентных штаммов бактерий. Быстрая эволюция резистентности бактерий к антимикробным препаратам является серьезным вызовом для современного здравоохранения, обусловливает необходимость создания новых антибиотических средств, а также активизации изучения молекулярных механизмов, лежащих в основе формирования устойчивости микроорганизмов. Одним из таких механизмов является бактериальная персистенция, которая проявляется образованием в микробной культуре клеток-персисторов, являющихся фенотипическим вариантом изогенной популяции. Персистенция бактерий может возникать самопроизвольно, независимо от воздействия антимикробных средств или причин, связанных с окружающей средой (недостаток питательных веществ, окислительный стресс или гипоксия). Эта небольшая по численности генерация клеток способна сохранять жизнеспособность даже в присутствии антимикробных средств в концентрациях, многократно превышающих терапевтические. Наличие в организме персисторных клеток патогенных бактерий снижает эффективность антибиотического лечения не в связи с генотипической лекарственной устойчивостью микроорганизма, а вследствие наличия фенотипической резистентности клеток-персисторов. Различие принципиальное, поскольку персисторы нечувствительны ко всем антибиотикам и для их эрадикации необходима разработка принципиально новых антимикробных стратегий. Клетки-персисторы представляют собой фенотипические варианты материнской культуры бактерий, которые присутствуют во всех популяциях микроорганизмов, а после наступления благоприятных условий способны рекультивироваться и сформировать новую генерацию вегетативных бактерий. В обзоре рассмотрены современные концепции молекулярно-генетических механизмов персистенции бактерий с акцентом на их клиническом значении для возникновения персистирующих инфекций, а также обсуждаются инновационные технологии эрадикации устойчивых клеточных форм микроорганизмов.

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Journal of microbiology, epidemiology and immunobiology. 2020; 97: 271-279

Molecular Mechanisms оf Persistence оf Bacteria

Andryukov Boris G., Lyapun Irina N.

https://doi.org/10.36233/0372-9311-2020-97-3-10

Abstract

A significant mortality rate from infectious diseases is largely mediated by the widespread and uncontrolled use of antibiotics, which has led to the emergence of drug-resistant strains of bacteria. The rapid evolution of bacterial resistance to antimicrobials is a serious challenge for modern health care, mediates the need to create new antibiotic agents, as well as to intensify the study of molecular mechanisms underlying the formation of microorganism resistance. One of these mechanisms is bacterial persistence, manifested by the formation of persistent cells in the culture, which are a phenotypic variant of the isogenic population. The persistence of bacteria can occur spontaneously, regardless of exposure to antimicrobials or environmental reasons, such as lack of nutrients, oxidative stress or hypoxia. This small cell subpopulation is able to maintain viability even in the presence of antimicrobial agents at concentrations many times higher than therapeutic. The presence of persistent cells of pathogenic bacteria in the host organism reduces the effectiveness of antibiotic treatment, not due to the genotypic drug resistance of the microorganism, but due to the presence of phenotypic resistance of persister cells. The difference is fundamental, since cell-persisters are insensitive to any antibiotics and the development of fundamentally new antimicrobial strategies is necessary for their eradication. Persister cells are phenotypic variants of the maternal culture of bacteria that are present in all populations of microorganisms, and after the onset of favorable conditions, they are able to reclaim and form a new generation of vegetative bacteria. This review discusses modern concepts of the molecular genetic mechanisms of bacterial persistence with an emphasis on their clinical significance for the occurrence of persistent infections, and discusses innovative technologies for the eradication of resistant cell forms of microorganisms.

References