Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang Province, China.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
J Antimicrob Chemother. 2024 Nov 4;79(11):2965-2974. doi: 10.1093/jac/dkae314.
To investigate the characteristics and clonal dynamics of tigecycline-resistant Acinetobacter baumannii (TRAB) isolates from a Chinese hospital from 2016 to 2021.
A total of 64 TRAB isolates were screened and WGS was performed. Phylogenetic analysis and non-polymorphic mutation analysis were used to analyse their clonal dynamics and tigecycline resistance-related mutations. RT-PCR was used to analyse the expression of the resistance-nodulation cell-division (RND) efflux pump genes adeB and adeJ. Gene cloning was used to explore the effect of tet(39) variants on tigecycline resistance.
Most TRAB isolates were found to be MDR, with 95% (61/64) of the isolates showing resistance to carbapenems. These TRAB isolates were classified into three primary genetic clusters based on core-genome SNPs. The KL2 cluster persisted throughout the study period, whereas the KL7 cluster emerged in 2019 and became the dominant clone. The KL7 cluster carried more antimicrobial resistance genes than the other two clusters. The predominant tigecycline resistance mechanism of the KL2 cluster and KL7 cluster was IS insertion in adeN (82.1%, 23/28) and genetic alterations in adeS (76.2%, 16/21), respectively. Eleven novel AdeS mutations were identified associated with elevated AdeB expression and tigecycline resistance. Moreover, we characterized a plasmid-borne tet(39) variant with an Ala-36-Thr substitution that synergizes with the RND efflux pump to confer high-level tigecycline resistance.
This work provides important insights into the diverse mechanisms associated with tigecycline resistance in A. baumannii, highlighting a pressing need for further monitoring of ST2-KL7 A. baumannii in clinical settings.
研究 2016 年至 2021 年中国某医院分离的替加环素耐药鲍曼不动杆菌（TRAB）的特征和克隆动态。
筛选了 64 株 TRAB 分离株进行 WGS，并进行了系统发育分析和非多态性突变分析，以分析其克隆动态和替加环素耐药相关突变。RT-PCR 用于分析耐药性-结节-分裂（RND）外排泵基因 adeB 和 adeJ 的表达。基因克隆用于探索 tet(39)变体对替加环素耐药的影响。
大多数 TRAB 分离株为 MDR，其中 95%（61/64）对碳青霉烯类药物耐药。这些 TRAB 分离株根据核心基因组 SNPs 分为三个主要遗传群。KL2 群在整个研究期间持续存在，而 KL7 群在 2019 年出现并成为主要克隆。KL7 群携带的抗菌药物耐药基因多于其他两个群。KL2 群和 KL7 群主要的替加环素耐药机制分别为 adeN 中 IS 插入（82.1%，23/28）和 adeS 基因的遗传改变（76.2%，16/21）。鉴定出 11 种与 AdeB 表达升高和替加环素耐药相关的新型 AdeS 突变。此外，我们还对携带 Ala-36-Thr 取代的质粒源性 tet(39)变体进行了特征分析，该变体与 RND 外排泵协同作用，赋予高水平的替加环素耐药性。
本研究为鲍曼不动杆菌替加环素耐药相关机制的多样性提供了重要见解，突显了在临床环境中进一步监测 ST2-KL7 鲍曼不动杆菌的迫切需要。
