Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1802410.15789/10.15789/2220-7619-EOE-18024ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИUnknownEFFECT OF EFFLUX PUMP EXPRESSION ON ANTIBIOTIC SENSITIVITY PATTERNS IN PSEUDOMONAS AERUGINOSA: PHENOTYPIC AND GENOTYPIC PROFILING OF CLINICAL ISOLATESВЛИЯНИЕ ЭКСПРЕССИИ ЭФФЛЮКС-НАСОСА НА ХАРАКТЕРИСТИКИ ЧУВСТВИТЕЛЬНОСТИ К АНТИБИОТИКАМ У PSEUDOMONAS AERUGINOSA: ФЕНОТИПИЧЕСКОЕ И ГЕНОТИПИЧЕСКОЕ ПРОФИЛИРОВАНИЕ КЛИНИЧЕСКИХ ИЗОЛЯТОВAbdullahAbdАбдуллаА.
Pakistan

M.Phil student

магистр философии, студент

abdulshinwari4@gmail.comBashirKashifБаширК.
Pakistan

PhD

Lecturer

доктор философии, преподаватель

kashif.bashir@abasyn.edu.pkKhanAbdul WaheedХанАбдул Вахид
Pakistan

PhD, Student

доктор философии, студент

awk780@gmail.comKhanMohebХанМохеб
China

PhD Student

доктор философии, исследователь

moheb.khan24@gmail.comTariqZarkishТарикЗ.
Pakistan

BS Zoology

Mphil Scholar

студент

zarkishtariq8090@gmail.comhttps://orcid.org/0009-0004-3872-4167NiazFalakНиазФалак
Pakistan

Mphil

student

магистр наук

falaknaz@riphah.ede.pkRehmanFaiz UrРехманФаиз Ур
Pakistan

M.Phil, Lecturer

магистр филологии, преподаватель

faiz02140@gmail.comAbasyn University, Khyber Pakhtunkhwa, Peshawar, PakistanУниверситет Абасин, Хайбер-Пахтунхва, Пешавар, ПакистанInstitute of Biotechnology & Microbiology, Bacha Khan University, Charsadda, PakistanИнститут биотехнологии и микробиологии, Университет Бача Хана, Чарсадда, ПакистанCenter for Circadian Clocks, Soochow University, Suzhou, Jiangsu, ChinaЦентр циркадных ритмов, Сучжоуский университет, Сучжоу, Цзянсу, КитайUniversity of Science and Technology, Bannu, Khyber Pakhtunkhwa, PakistanУниверситет науки и технологий, Банну, Хайбер-Пахтунхва, ПакистанRiphah International University, Malakand Campus Chakdara, Khyber Pakhtunkhwa, PakistanМеждународный университет Рифах, кампус Малаканд, Чакдара, Хайбер-Пахтунхва, ПакистанGovernment Superior Science College Peshawar, Khyber Pakhtunkhwa, PakistanГосударственный высший научный колледж, Пешавар, Хайбер-Пахтунхва, Пакистан060320262709202505032026Copyright ©; , ullah A., Bashir K., Rehman F., wali K., Khan A., Syed W., Harbi K.Copyright ©; , ullah A., Bashir K., Rehman F., wali K., Khan A., Syed W., Harbi K.ullah A., Bashir K., Rehman F., wali K., Khan A., Syed W., Harbi K.ullah A., Bashir K., Rehman F., wali K., Khan A., Syed W., Harbi K.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/18024

Pseudomonas aeruginosa is an opportunistic pathogen of significant global health concern, largely due to its escalating resistance to multiple antibiotics. A major mechanism contributing to its multidrug resistance (MDR) phenotype is the overexpression of efflux pump systems, particularly the mexAB-OprM complex. This study aimed to assess the prevalence, antibiotic susceptibility patterns, and phenotypic and genotypic profiles of efflux pump-mediated resistance in P. aeruginosa clinical isolates.

One hundred clinical specimens were collected from Al-Khidmat Hospital. Antibiotic susceptibility was tested against ten antibiotics using the Kirby-Bauer method, while efflux pump activity was assessed via the ethidium bromide–agar cartwheel method. Genotypic detection of mexA and mexB genes was performed by PCR.

Forty percent of clinical samples yielded bacterial growth, with P. aeruginosa isolates more prevalent in males (54%). High resistance rates were observed against several commonly used antibiotics, particularly cephalosporins, fluoroquinolones, ceftazidime (82%), ciprofloxacin (70%), cefepime (61%) and levofloxacin (66%). In contrast, imipenem (76%), amikacin (73%) and gentamicin (70%) colistin showing (100%) susceptibility demonstrated comparatively higher susceptibility. Among the isolates, 62.5% were classified as MDR strains. Notably, 68% of MDR isolates exhibited phenotypic efflux pump activity. Genotypic analysis confirmed the widespread presence of efflux pump genes, with 71% and 82% of MDR isolates positive for mexA and mexB, respectively. Efflux pump overexpression, particularly involving mexA and mexB is a major driver of MDR in P. aeruginosa. The widespread detection of these genes provides strong genetic evidence that the mexAB-OprM efflux system is the dominant resistance mechanism in this population. These findings underscore the need for routine molecular surveillance of efflux activity in clinical diagnostics and highlight the therapeutic potential of efflux pump inhibitors (EPIs). Combining otherwise resistance antibiotics, such as ciprofloxacin or ceftazidime, with EPIs may restore their efficacy and expand treatment options for MDR infections. Overall, the results emphasize the importance of antibiotic stewardship, targeted resistance monitoring and the development of EPI–antibiotic combinations as future strategies to manage P. aeruginosa resistance.

Pseudomonas aeruginosa — условно-патогенный микроорганизм, представляющий существенную мировую угрозу для здоровья, главным образом из-за растущей мультирезистентности к антибиотикам. Одним из основных механизмов, способствующих развитию фенотипа множественной лекарственной устойчивости (МЛУ), является гиперэкспрессия систем эффлюксных насосов, в частности комплекса mexAB-OprM. Целью данного исследования было оценить распространенность, особенности чувствительности к антибиотикам, а также фенотипические и генотипические профили резистентности, опосредованной эффлюксными насосами, в клинических изолятах P. aeruginosa.

Было изучены сто клинических образцов из больницы Аль-Хидмат еа чувствительность к десяти антибиотикам с применением метода Кирби-Бауэра. Активность эффлюксных насосов оценивали методом метод «колеса тележки» на агаре с бромидом этидия (EtBr). Генотипическое определение генов mexA и mexB проводили методом ПЦР.

В 40% клинических образцов наблюдался рост бактерий, при этом изоляты P. aeruginosa чаще встречались у мужчин (54%). Высокий уровень резистентности наблюдался к нескольким распространенным антибиотикам, в частности к цефалоспоринам, фторхинолонам, цефтазидиму (82%), ципрофлоксацину (70%), цефепиму (61%) и левофлоксацину (66%). В отличие от этого, имипенем (76%), амикацин (73%) и гентамицин (70%), а также колистин (100%) продемонстрировали сравнительно более высокую чувствительность. Среди изолятов 62,5% были классифицированы как мультирезистентные штаммы (MDR). Примечательно, что 68% MDR-изолятов проявляли фенотипическую активность эффлюксных насосов. Генотипический анализ подтвердил широкую представленность генов эффлюксных насосов: 71% и 82% MDR-изолятов были положительными на наличие генов mexA и mexB соответственно. Гиперэкспрессия эффлюксных насосов, особенно mexA и mexB, является главным фактором развития множественной лекарственной устойчивости (МЛУ) у P. aeruginosa. Выраженная представленность этих генов служит убедительным генетическим доказательством того, что система эффлюкса mexAB-OprM является доминирующим механизмом резистентности. Полученные результаты подчеркивают необходимость рутинного молекулярного мониторинга активности эффлюксных насосов в клинической диагностике и указывают на терапевтический потенциал ингибиторов эффлюксных насосов (ИЭН). Комбинирование антибиотиков без устойчивости, таких как ципрофлоксацин или цефтазидим, с ИЭН может восстановить их эффективность и расширить возможности лечения инфекций с МЛУ. В целом, результаты подчеркивают важность рационального использования антибиотиков, целенаправленного мониторинга резистентности и разработки комбинаций ИЭН-антибиотиков в качестве перспективных стратегий борьбы с резистентными P. aeruginosa.

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