Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC880710.15690/vramn8807PHTHISIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ФТИЗИАТРИИResearch ArticleDrug-Resistant Tuberculosis: Development Mechanisms and Methods of Molecular Genetic DiagnosisТуберкулез с лекарственной устойчивостью возбудителя: механизмы формирования и методы молекулярно-генетической диагностикиhttps://orcid.org/0000-0002-2494-9275ErgeshovAtadzhan E.ЭргешовАтаджан Эргешович
Russian Federation

MD, PhD, Professor, Corresponding Member of the RAS

д.м.н., профессор, член-корреспондент РАН

ctri@ctri.ruhttps://orcid.org/0000-0002-4589-6133AndreevskayaSofya N.АндреевскаяСофья Николаевна
Russian Federation

MD, PhD, Senior Researcher

к.м.н., старший научный сотрудник

andsofia@mail.ruhttps://orcid.org/0000-0003-2886-1745SmirnovaTatyana G.СмирноваТатьяна Геннадьевна
Russian Federation

MD, PhD

к.м.н.

s_tatka@mail.ruhttps://orcid.org/0000-0001-6288-7549ChernousovaLarisa N.ЧерноусоваЛариса Николаевна
Russian Federation

PhD in Biology, Professor

д.б.н., профессор

lchernousova@mail.ruCentral TB Research InstituteЦентральный научно-исследовательский институт туберкулезаA.I. Evdokimov Moscow State University of Medicine and DentistryМосковский государственный медико-стоматологический университет имени А.И. Евдокимова231220237866096200205202301122023Copyright ©; 2023, "Paediatrician" Publishers LLCCopyright ©; 2023, Издательство "Педиатръ"2023"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/8807

The widespread occurrence of drug-resistant tuberculosis is an important public health challenge. To better understand this phenomenon, the article summarizes current ideas on the development of mechanisms of Mycobacterium tuberculosis resistance to antituberculosis drugs. Special attention is paid to the mechanism of acquired resistance based on mutations in the genes encoding antituberculosis drug targets or enzymes that translate pro-drug into its active form; the effect of these mutations on fitness of the pathogen is in the focus of the article. It emphasizes the leading role of molecular genetic methods for diagnosing M. tuberculosis drug resistance and importance of these methods for preventing the expansion of the pathogen’s resistance range and the spread of resistant clones in the population. A comparison of sequencing and PCR-based methods capacities led to a conclusion that at the current stage of technological development it is reasonable to use each of these approaches for specific purposes: domestic PCR-based tests — for diagnosis, and sequencing — for basic research of M. tuberculosis evolution and epidemiological monitoring. Promising areas of M. tuberculosis resistance research were proposed to develop new approaches for diagnosis and treatment of drug-resistant tuberculosis and to provide effective personalized therapy.

Широкое распространение туберкулеза с лекарственной устойчивостью возбудителя — важная проблема общественного здравоохранения. Для лучшего понимания этого явления в статье суммируются современные представления о механизмах формирования устойчивости Mycobacterium tuberculosis к противотуберкулезным препаратам. Особое внимание уделяется механизму приобретенной резистентности, основанному на мутациях в генах, кодирующих мишени противотуберкулезных препаратов, или ферменты, переводящие пролекарство в активную форму, рассматривается влияние этих мутаций на возбудителя. В статье сделан акцент на ведущей роли молекулярно-генетических методов для диагностики лекарственной устойчивости M. tuberculosis и подчеркивается значимость этих методов для предотвращения расширения спектра резистентности возбудителя и профилактики распространения устойчивых клонов в популяции. Сравнение возможностей секвенирования и методов, основанных на ПЦР, позволило заключить, что на современном этапе развития технологий каждый из этих подходов целесообразно использовать для решения конкретных задач: отечественные тесты, основанные на ПЦР, — для ежедневной диагностики, а секвенирование — для фундаментальных исследований в области эволюции M. tuberculosis и эпидемиологического мониторинга. Предложены перспективные направления исследований резистентности M. tuberculosis, которые позволят выработать новые подходы для диагностики и лечения туберкулеза с лекарственной устойчивостью возбудителя и обеспечить эффективную персонализированную терапию.

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