Подбор новых молекулярных мишеней для оптимизации вакцинопрофилактики и терапии чумы

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Возбудитель чумы, Yersinia pestis, — особо опасный бактериальный патоген и потенциальный агент биотерроризма. Преобладающими клиническими формами инфекции являются бубонная и легочная чума, отличающиеся путем инфицирования. При отсутствии лечения смертность при бубонной форме чумы составляет 40—60%, в то время как легочная чума без лечения летальна всегда. Развитие инфекционного процесса в организме восприимчивого хозяина обеспечивается наличием у чумного микроба комплекса факторов патогенности различной функциональной направленности, экспрессирующихся в зависимости от стадии инфекционного процесса. Нокаутные мутации генов, кодирующих эти факторы, могут не влиять на вирулентность микроба или приводить к его аттенуации. Поиск новых факторов патогенности Y. pestis и разработка на их основе высокоэффективных субъединичных и живых чумных вакцин, индуцирующих развитие выраженных клеточных и гуморальных иммунных реакций, и/или оценка потенциального использования этих факторов в качестве молекулярных мишеней для химиотерапии чумы остаются по-прежнему актуальными, так как обе лицензированные на настоящий день чумные вакцины не соответствуют требованиям ВОЗ, а на Мадагаскаре выделены штаммы чумного микроба, устойчивые ко всем лекарственным препаратам, рекомендованным для антибактериальной терапии чумы. В настоящей статье обобщены сведения относительно вклада известных и вновь открытых факторов патогенности в вирулентность штаммов Y. pestis и протективную активность в отношении чумы. Описано также влияние утраты генов регуляторных белков и мутаций в генах различных транспортных систем Y. pestis на аттенуацию вирулентных штаммов. Проведена оценка перспективности включения охарактеризованных антигенов в состав прототипов субъединичных вакцин и тех или иных полученных мутантов в состав прототипов живых аттенуированных вакцин. Использование антибиотиков постулируется комитетом экспертов Всемирной организации здравоохранения по чуме как «золотой стандарт» лечения чумы. Однако появление устойчивых к антибиотикам штаммов Y. pestis привело к необходимости поиска альтернативных способов терапии. В обзоре обобщены предварительные результаты попыток лечения чумы ингибиторами фактора патогенности. Препараты, нацеленные на ключевые факторы патогенности, предоставляют новые перспективные возможности в борьбе с устойчивыми к антибиотикам бактериями.

Об авторах

Е. А. Красильникова

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Email: krasilnikowa.katya111@yandex.ru

Младший научный сотрудник лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

Россия

А. С. Трунякова

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Email: Sasha_trunyakova@mail.ru
ORCID iD: 0000-0001-9223-2105

Стажер-исследователь лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

SPIN-код: 7290-1420

Россия

А. С. Вагайская

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Email: vagaiskaya.anastasiya@gmail.com
ORCID iD: 0000-0001-7280-3660

Младший научный сотрудник лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

Россия

Т. Э. Светоч

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Email: tanyasvetoch@yandex.ru

Научный сотрудник лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

Россия

Р. З. Шайхутдинова

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Email: shaikhutdinova@yandex.ru
ORCID iD: 0000-0002-6985-6822

Старший научный сотрудник лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

Россия

С. В. Дентовская

Государственный научный центр прикладной микробиологии и биотехнологии Роспотребнадзора

Автор, ответственный за переписку.
Email: dentovskaya@yandex.ru
ORCID iD: 0000-0002-1996-8949

Дентовская Светлана Владимировна - доктор медицинских наук, главный научный сотрудник лаборатории микробиологии чумы отдела особо опасных инфекций.

142279, Московская область, Серпуховский р-н, п. Оболенск.

Тел.: 8 (4967) 36-01-17

SPIN-код: 4861-5248

Россия

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© Красильникова Е.А., Трунякова А.С., Вагайская А.С., Светоч Т.Э., Шайхутдинова Р.З., Дентовская С.В., 2020

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