УСТОЙЧИВОСТЬ MYCOBACTERIUM TUBERCULOSIS К ПИРАЗИНАМИДУ/ПИРАЗИНОЕВОЙ КИСЛОТЕ: НОВЫЕ СВЕДЕНИЯ И ИХ ЗНАЧЕНИЕ ДЛЯ ПОВЫШЕНИЯ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА

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Аннотация

Резюме. Пиразинамид (PZA) уникален тем, что является противотуберкулезным препаратом первого ряда как при лечении лекарственно-чувствительного туберкулеза, так и компонентом современных курсов лечения мультирезистентного туберкулеза. Также было показано, что PZA помогает обеспечить длительное лечение и предотвратить рецидив в более коротких схемах приема нескольких лекарств. Пиразинамид является неактивным пролекарством и фермент PncA Mycobacterium tuberculosis превращает его в активную форму — пиразиноевую кислоту (POA). Большинство клинических PZA-резистентных штаммов содержат мутации внутри гена pncA и поэтому остаются восприимчивыми к POA, поскольку не активируют PZA. Устойчивость к активному соединению POA требует альтернативного механизма резистентности, и полученные in vitro POA-резистентные спонтанные мутанты MTB имеют ряд мутаций в гене panD или в серии генов, большинство из которых связаны с регуляцией строгого ответа бактерий. Клинические штаммы MTB, устойчивые к PZA и POA с мутациями в любом из этих генов, являются нетипичными. Таким образом, вероятно, строгий ответ имеет важное значение для MTB в условиях in vivo, а нарушенный ответ приводит к снижению жизнеспособности микроорганизма. Были идентифицированы различные лекарственные соединения-прототипы, нарушающие строгий ответ MTB, которые могут стать основой для препаратов с активностью против латентных форм микобактерий с целью сокращения сроков противотуберкулезного лечения. В данном обзоре мы обсуждаем роль латентного периода в жизненном цикле MTB и возможные связи с активностью PZA с особым вниманием к потенциально новым мишенями и препаратам.

Об авторах

Р. М. Энтони

Национальный институт общественного здоровья и окружающей среды, г. Билтховен

Автор, ответственный за переписку.
Email: richard.anthony@rivm.nl

старший научный сотрудник

а/я 1, 3720 БА Билтховен, Нидерланды, Национальный институт
общественного здоровья и окружающей среды.
Тел.: +31302742363. Факс: +31302744418

Нидерланды

А. Л. Ден Хертог

Институт медико-биологических наук и химии, Университет прикладных наук, г. Утрехт

Email: fake@neicon.ru
преподаватель Нидерланды

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