Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI182510.15789/2220-7619-COM-1825REVIEWSОБЗОРЫReview ArticleConvergence of multiple resistance and hypervirulence in Klebsiella pneumoniaeКонвергенция множественной резистентности и гипервирулентности у Klebsiella pneumoniaehttps://orcid.org/0000-0002-3963-0144AgeevetsVladimir A.АгеевецВладимир Андреевич
Russian Federation

PhD (Biology), Researcher, Research Department of Medical Microbiology and Molecular Epidemiology

к.б.н., научный сотрудник научно-исследовательского отдела медицинской микробиологии и молекулярной эпидемиологии

ageevets@list.ruhttps://orcid.org/0000-0002-3549-3525AgeevetsI. V.АгеевецИ. В.
Russian Federation

PhD (Medicine), Researcher, Research Department of Medical Microbiology and Molecular Epidemiology

к.м.н., научный сотрудник научно-исследовательского отдела медицинской микробиологии и молекулярной эпидемиологии

partina-irina@yandex.ruhttps://orcid.org/0000-0003-3550-7875SidorenkoS. V.СидоренкоС. В.
Russian Federation

PhD, MD (Medicine), Professor, Head of the Research Department of Medical Microbiology and Molecular Epidemiology

д.м.н., профессор, зав. научно-исследовательским отделом медицинской микробиологии и молекулярной эпидемиологии

sidorserg@gmail.comPaediatric Research and Clinical Centre for Infectious DiseasesФГБУ Детский научно-клинический центр инфекционных болезней ФМБА РоссииPaediatric Research and Clinical Centre for Infectious Diseases,ФГБУ Детский научно-клинический центр инфекционных болезней ФМБА России12042022040720221234504601711202128012022Copyright ©; 2022, Ageevets V.A., Ageevets I.V., Sidorenko S.V.Copyright ©; 2022, Агеевец В.А., Агеевец И.В., Сидоренко С.В.2022Ageevets V.A., Ageevets I.V., Sidorenko S.V.Агеевец В.А., Агеевец И.В., Сидоренко С.В.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1825

Since 2018, Klebsiella pneumoniae isolates have been described in Russia, demonstrating the convergence of hypervirulent properties and multiple antibiotic resistance. The problem of the Klebsiella hypervirulent pathotype has been actualized relatively recently that was progressively described in the 1980s in the Pacific region. These Klebsiella spp. can cause serious community-acquired infections in healthy people, which fundamentally differs from the classic Klebsiella pathotype initially preserving sensitivity to most antibacterial drugs. In 2018–2020, there were reported detection of hypervirulent K. pneumoniae isolates in the Russian Federation. Like multiple resistance, hypervirulence is associated with the acquiring additional genetic material and formation of genetic lineages that effectively support such acquired determinants. For a long time, it was believed that the convergence of multiple resistance and hypervirulence is unlikely due to a large genetic burden as well as different ecological strategies in same species. The spread of hypervirulent strains, primarily in the Asian region, is associated with the conserved plasmids of the pLVPK “group”. The conservatism of both the originally discovered virulence plasmids (such as pLVPK and pK2044) and the genetic lineages associated with them (mainly CG23) is probably determined by the absence of a gene cluster responsible for conjugation in these plasmids. The driver of the spread of non-conjugative plasmids with determinants of hypervirulence is clonal spread, not horizontal gene transfer. Nevertheless, after a sufficiently long period of circulation of plasmids bearing markers of hypervirulence (described since 1986) in Klebsiella, a relatively limited number of genetic lineages, there were events of mobilization of the determinants of hypervirulence and, as a consequence, the inclusion in horizontal gene transfer in the population (described cases in 2016 ), which led to a sharp increase in the number of genetic lineages and variants of genetic platforms carrying hypervirulence genes. In Russia, first cases of hv-MDR-Kpn were described in 2018 in Moscow based on analyzing collection of Klebsiella isolated in 2012–2016. In 2020 and 2021, similar cases were described in St. Petersburg. In case of repeated pessimistic scenario observed over the last decade due to spread of carbapenemases, effectiveness of health care will be more than substantially harmed.

Начиная с 2018 г. в России описываются изоляты Klebsiella pneumoniae, демонстрирующие конвергенцию гипервирулентных свойств и множественной резистентности к антибиотикам. Проблема гипервирулентного патотипа клебсиелл актуализирована относительно недавно, его начали описывать в восьмидесятых годах в Тихоокеанском регионе. Эти клебсиеллы способны вызывать серьезные внебольничные инфекции у здоровых людей, чем принципиально отличаются от клебсиелл классического патотипа, и изначально они сохраняли чувствительность к большинству антибактериальных препаратов. В 2018–2020 гг. появились сообщения о выделении гипервирулентных изолятов K. pneumoniae в Российской Федерации. Гипервирулентность, так же как и множественная резистентность, связана с приобретением дополнительного генетического материала и формированием генетических линий, эффективно поддерживающих эти приобретенные детерминанты. Долгое время было принято считать, что конвергенция свойств множественной резистентности и гипервирулентности маловероятна из-за слишком большого генетического груза, а также разных экологических стратегий одного вида. Распространение гипервирулентных штаммов, в первую очередь, в азиатском регионе, связано с консервативными плазмидами «группы» pLVPK. Консервативность как самих первоначально обнаруженных плазмид вирулентности (типа pLVPK и pK2044), так и генетических линий с ними связанных (преимущественно CG23), вероятно, определяется отсутствием у данных плазмид кластера генов, отвечающих за конъюгацию. Драйвером распространения неконъюгативных плазмид с детерминантами гипервирулентности является клональное распространение, а не горизонтальный перенос генов. Тем не менее после достаточно долгого периода циркуляции плазмид с маркерами гипервирулентности (описываются начиная с 1986 г.) у клебсиелл некоторых генетических линий, произошли события мобилизации детерминант гипервирулентности и, как следствие, включение их в горизонтальный перенос генов в популяции (описанные случаи в 2016 г.), что привело к резкому расширению числа генетических линий и вариантов генетических платформ, несущих гены гипервирулентности. Первые случаи в России hv-MDR-Kpn описаны в 2018 г. в Москве на основе анализа коллекции клебсиелл, собранных в 2012–2016 гг. В 2020 и 2021 гг. описаны подобные случаи в Санкт-Петербурге. В случае повторения пессимистичного сценария, который наблюдался последние десять лет в связи с распространением карбапенемаз, эффективности здравоохранения будет нанесен более чем существенный вред.

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