AdeABC, AdeFGH, and AdeIJK efflux pumps as key factors in tigecycline resistance of Acinetobacter baumannii: a study from Western Balkan hospitals.

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES
Katarina Novović, Milica Radovanović, Ina Gajić, Zorica Vasiljević, Milka Malešević, Katarina Šapić, Branko Jovčić
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引用次数: 0

Abstract

Purpose: The present study investigated the role of resistance-nodulation-cell division (RND) efflux pumps in tigecycline resistance of Acinetobacter baumannii clinical isolates recovered from three Western Balkan countries (Serbia, Bosnia and Herzegovina and Montenegro).

Methods: A total of 37 A. baumannii isolates recovered from seven tertiary care hospitals in 2016 and 2022 were tested against tigecycline using broth microdilution method. Then, efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was used to determine the involvement of efflux pumps in tigecycline resistance. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multiplex PCR-based determination of clonal lineage. Regulators of efflux pumps were analyzed for amino acid substitutions, while reverse transcription-quantitative PCR (RT-qPCR) enabled quantification of RND efflux pumps expression.

Results: All tested isolates were interpreted as resistant to tigecycline and showed reduced tigecycline minimum inhibitory concentration (MIC) values in the presence of CCCP. PFGE analysis showed significant diversity among isolates grouped in cluster I including IC2 (n = 32) and IC3 (n = 1) isolates, while cluster II was comprised of four IC1 isolates. The most prevalent substitutions in AdeR were V120I and A136V and in AdeS G186V and N268H (n = 33). The Q262R substitution was detected in AdeL proteins of IC1 isolates, whereas no alterations were observed within AdeN. The expression of the adeB, adeG, and adeJ genes in selected isolates was upregulated in five (1.16- to 3-fold), sixteen (1.35- to 2.82-fold), and twelve isolates (1.62- to 4-fold) compared to ATCC19606, respectively.

Conclusion: This study revealed that overexpression of RND efflux pumps underlies tigecycline resistance in A. baumannii clinical isolates from the Western Balkans.

作为鲍曼不动杆菌耐替加环素关键因素的 AdeABC、AdeFGH 和 AdeIJK 外排泵:一项来自西巴尔干半岛医院的研究。
目的:本研究调查了耐药性-结节细胞分裂(RND)外排泵在从三个西巴尔干国家(塞尔维亚、波斯尼亚和黑塞哥维那以及黑山)回收的鲍曼不动杆菌临床分离株对替加环素耐药性中的作用:方法:采用肉汤微稀释法对2016年和2022年从7家三级医院分离的37株鲍曼不动杆菌进行了替加环素耐药性测试。然后,使用外排泵抑制剂3-氯苯基腙(CCCP)来确定外排泵在替加环素耐药性中的参与情况。通过脉冲场凝胶电泳(PFGE)和基于多重 PCR 的克隆谱系测定进行了分子分型。分析了外排泵调节剂的氨基酸替代情况,同时通过反转录定量 PCR(RT-qPCR)对 RND 外排泵的表达进行了定量:结果:所有检测的分离物都被认为对替加环素具有耐药性,并且在 CCCP 存在的情况下,替加环素的最低抑菌浓度 (MIC) 值都有所降低。PFGE 分析表明,被归入簇 I 的分离物之间存在明显的多样性,其中包括 IC2(n = 32)和 IC3(n = 1)分离物,而簇 II 则由 4 个 IC1 分离物组成。AdeR中最常见的置换是V120I和A136V,AdeS中最常见的置换是G186V和N268H(n = 33)。在 IC1 分离物的 AdeL 蛋白中检测到了 Q262R 取代,而在 AdeN 中未观察到任何改变。与 ATCC19606 相比,所选分离株中 adeB、adeG 和 adeJ 基因的表达分别上调了 5 个(1.16-3 倍)、16 个(1.35-2.82 倍)和 12 个(1.62-4 倍):本研究发现,RND外排泵的过度表达是西巴尔干半岛鲍曼不动杆菌临床分离株对替加环素产生耐药性的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.40
自引率
2.20%
发文量
138
审稿时长
1 months
期刊介绍: EJCMID is an interdisciplinary journal devoted to the publication of communications on infectious diseases of bacterial, viral and parasitic origin.
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