Overexpression of AdeABC efflux pump associated with tigecycline resistance in clinical Acinetobacter nosocomialis isolates
Overexpression of AdeABC efflux pump associated with tigecycline resistance in clinical Acinetobacter nosocomialis isolates
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DOI：
10.1016/j.cmi.2018.06.012
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发表时间：
2019-04-01
影响因子：
14.2
通讯作者：
Yang, Ya-Sung
中科院分区：
文献类型：
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作者：
Yang, Y-S;Chen, H-Y;Yang, Ya-Sung
目的：在临床分离株中发现替加环素不敏感的院内不动杆菌 (TNAN)。抗性结节细胞分裂（RND）型外排系统在替加环素不敏感的鲍曼不动杆菌中起主要作用，但在院内不动杆菌中的机制仍不清楚。我们的目的是分析从台湾多个医疗中心收集的临床放线菌分离株中基于外排的替加环素耐药性的贡献。方法：对总共 57 株医院放线菌分离株进行了分析，其中包括 46 株 TNAN 和 11 株对替加环素敏感的医院放线菌 (TSAN) 分离株。其中，46 个 TNAN 分离株通过多位点序列分型聚类为 ST410（43 个分离株）和 ST68（3 个分离株）。 结果：通过使用外排泵抑制剂 NMP 成功降低替加环素耐药性，间接验证了 RND 外排泵与替加环素耐药性之间的关系。在所有临床分离株中均检测到了三种 RND 外排系统（AdeABC、AdeIJK 和 AdeFGH）。 adeB基因转录水平显着升高，且与替加环素耐药性相关。此外，考虑到氨基酸序列，AdeRS双组分系统进一步分为四种不同类型的AdeRS模式。进一步分析发现替加环素耐药性与adeB基因的转录水平和AdeRS模式有关。结论：本研究表明TNAN分离株在台湾的传播主要归因于ST410的传播。 AdeABC 外排泵似乎在院内放线菌的替加环素耐药性中发挥重要作用。 (C) 2018 年欧洲临床微生物学和传染病学会。由爱思唯尔有限公司出版。保留所有权利。
Objectives: Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan.Methods: A total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing.Results: The relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern.Conclusion: This study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.