Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI55510.15789/2220-7619-2017-3-231-244REVIEWSОБЗОРЫMOLECULAR BACKGROUND OF FLUOROQUINOLONE RESISTANCE IN PATHOGENIC HUMAN MYCOPLASMASМОЛЕКУЛЯРНЫЕ ОСНОВЫ УСТОЙЧИВОСТИ ПАТОГЕННЫХ ДЛЯ ЧЕЛОВЕКА МИКОПЛАЗМ К ФТОРХИНОЛОНАМVaganovaA. N.ВагановаА. Н.
Russian Federation

Anastasiya N. Vaganova - Junior Researcher, Laboratory of Biomolecular Technologies, Department of New Technologies/

197101, St. Petersburg, Mira str., 14, St. Petersburg Pasteur Institute. Phone: +7 (812) 232-01-08 (office)

Ваганова Анастасия Николаевна - младший научный сотрудник лаборатории молекулярно-биологических технологий отдела новых технологий.

197101, Санкт-Петербург, ул. Мира, 14. Тел.: 8 (812) 232-01-08 (служебн.)

van.inprogress@gmail.comSt. Petersburg Pasteur InstituteФБУН НИИ эпидемиологии и микробиологии имени Пастера29092017732312442909201729092017Copyright ©; 2017, Vaganova A.N.Copyright ©; 2017, Ваганова А.Н.2017Vaganova A.N.Ваганова А.Н.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/555

Human mycoplasma pathogens are resistant to many types of antibiotics because of the lack of a cell wall. Macrolides are most often used for the treatment of mycoplasmosis, but the spread of forms resistant to these antibiotics requires the use of alternative treatment regimens, in particular, the administration of f luoroquinolones and tetracyclines. Of the existing antimicrobial compounds, only f luoroquinolones have a bactericidal effect against mycoplasmas, so use of these antimicrobials is preferable for the treatment of immunosuppressed patients. The limitation of the f luoroquinolones is the resistance of the causative agent to these antimicrobials. Mutations leading to amino acid substitutions in the composition of the targets of f luoroquinolones, gyrase and topoisomerase IV are the most common cause of resistance to f luoroquinolones both in mycoplasms and in other bacteria. It was noted that for mycoplasmas belonging to different species have different patterns of substitutions in the subunits of gyrase and topoisomerase IV. The differences of the structure of these proteins, ref lected in the natural susceptibility to f luoroquinolones in mycoplasmas, may be a reason of this heterogeneity. A number of studies indicate the existence of additional resistance mechanisms, which, first of all, include multiple-resistance systems. Such systems belonging to the ABC-transporter group were also found in mycoplasmas. They are described in Mycoplasma hominis and M. pneumoniae, in M. hominis, their ability to excrete f luoroquinolones from the cells was observed, and in M. pneumoniae the ability of multiple-resistance systems to export macrolides also was noted. Genes encoding components of multiple resistance systems have been found in genomes of other species, including M. genitalium and mycoplasmas, causing animal diseases. Also, in the non-pathogenic for human mycoplasmas Acholeplasma laidlawii, the ability to export proteins and genetic material associated with resistance to f luoroquinolones was found. Understanding the role of the mutations, the activity of transports and their cumulative effect in the development of resistance to f luoroquinolones is particularly important in the context of the determination of resistance to f luoroquinolones in difficult to culture pathogens M. genitalium and M. pneumoniae. Molecular methods for determining the resistance to antimicrobials are now included in clinical practice, but the lack of information about the molecular bases of mycoplasma resistance makes the result insufficiently informative for the pathogens of this group. In the review, the features of the development of resistance to f luoroquinolones in various species of human pathogenic mycoplasmas and their mechanisms at molecular level will be described.

Патогенные для человека микоплазмы из-за отсутствия клеточной стенки устойчивы к ряду антибиотиков. Для лечения микоплазмозов чаще всего используют макролиды, однако распространение устойчивых к ним форм требует применения альтернативных схем лечения, в частности, назначения фторхинолонов и тетрациклинов. Из существующих противомикробных соединений только фторхинолоны обладают бактерицидным эффектом в отношении микоплазм, поэтому их применение предпочтительно при лечении пациентов в состоянии иммуносупрессии. Ограничением применения фторхинолонов может стать устойчивость возбудителя к соединениям данной группы. Наиболее частой причиной развития устойчивости к фторхинолонам как у микоплазм, так и у других бактерий являются мутации, ведущие к аминокислотным заменам в составе мишеней фторхинолонов: гиразы и топоизомеразы IV. Отмечено, что для микоплазм, относящихся к различным видам, характерны разные паттерны замен в субъединицах гиразы и топоизомеразы IV. Причиной могут быть различия в структуре этих белков, отражающиеся в видовых особенностях природной восприимчивости к фторхинолонам у микоплазм. Ряд исследований указывает на существование дополнительных механизмов резистентности, к которым, в первую очередь, относятся системы множественной резистентности. Подобные системы, относящиеся к группе ABC-транспортеров, были найдены и у микоплазм. Они описаны у Mycoplasma hominis и M. pneumoniae, причем у M. hominis наблюдалась их способность к выведению из клеток фторхинолонов, а у M. pneumoniae отмечена способность систем множественной резистенции экспортировать макролиды. Гены, кодирующие компоненты систем множественной резистентности, были найдены и в геномах других видов, в том числе M. genitalium и микоплазм, вызывающих заболевания животных. Также у непатогенных для человека микоплазм вида Acholeplasma laidlawii была обнаружена ассоциированная с устойчивостью к фторхинолонам способность к экспорту белков и генетического материала. Понимание роли мутаций, активности транспортеров и их кумулятивного эффекта в развитии устойчивости к фторхинолонам особенно важно в контексте определения устойчивости к фторхинолонам у плохо поддающихся культивированию патогенов M. genitalium и M. pneumoniae. Молекулярно-биологические методы определения устойчивости к противомикробным соединениям в настоящее время входят в клиническую практику, однако недостаток сведений о молекулярных основах устойчивости микоплазм делает результат недостаточно информативным для патогенов данной группы. В обзоре рассмотрены особенности развития устойчивости к фторхинолонам у патогенных для человека микоплазм разных видов и их проявления на молекулярном уровне.

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