Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
J Antimicrob Chemother. 2021 Dec 24;77(1):58-68. doi: 10.1093/jac/dkab375.
To characterize a novel plasmid-mediated tigecycline resistance-related gene, tet(Y), in a clinical Acinetobacter baumannii isolate from China.
The tet(Y)-encoded tigecycline-resistant A. baumannii 2016GDAB1 was screened through antimicrobial susceptibility testing and WGS. The function of tet(Y) was verified by complementation of tet(Y). The plasmid transferability and stability were detected via plasmid conjugation and in vitro bacterial passaging. The 3D structure of Tet(Y) was predicted and docked using tFold and AutoDock Vina.
The tigecycline-resistant A. baumannii 2016GDAB1 was isolated from bronchoalveolar lavage fluid of a patient with hospital-acquired pneumonia. However, this strain did not harbour any common tigecycline resistance genes, determinants or mutations. 2016GDAB1 belongs to the non-epidemic clone ST355 (Oxford scheme), which has been mainly reported in animals. The tet(Y) gene was located on a 72 156 bp plasmid and genomic environment analysis revealed that Tn5393 may play a role in tet(Y) transmission, whereas phylogenetic analysis indicated the origin of tet(Y) as from Aeromonas. Overexpression of tet(Y) resulted in a 2- to 4-fold increase in tigecycline MIC. Introduction of the tet(Y)-harbouring plasmid p2016GDAB1 via electroporation resulted in a 16-fold increase in tigecycline MIC but failed to transfer into the tigecycline-susceptible A. baumannii recipient via conjugation. Isolates carrying the tet(Y) gene were vulnerable to tigecycline pressure and exhibited decreased susceptibility to tigecycline. A tet(Y)-carrying plasmid was stably maintained in the host strains.
This study identified the tigecycline resistance-related gene tet(Y) in A. baumannii. This gene conferred an increased tigecycline MIC and the transposable element Tn5393 may play a role in its transmission across isolates.
从中国分离的临床鲍曼不动杆菌中鉴定一种新型质粒介导的替加环素耐药相关基因 tet(Y)。
通过药敏试验和 WGS 筛选替加环素耐药的鲍曼不动杆菌 2016GDAB1。通过互补 tet(Y)验证 tet(Y)的功能。通过质粒接合和体外细菌传代检测质粒的可转移性和稳定性。使用 tFold 和 AutoDock Vina 预测和对接 Tet(Y)的 3D 结构。
耐替加环素的鲍曼不动杆菌 2016GDAB1 从一名医院获得性肺炎患者的支气管肺泡灌洗液中分离得到。然而,该菌株不携带任何常见的替加环素耐药基因、决定簇或突变。2016GDAB1 属于非流行克隆 ST355(牛津方案),主要在动物中报道。tet(Y)基因位于一个 72156bp 的质粒上,基因组环境分析表明 Tn5393 可能在 tet(Y)传播中起作用,而系统发育分析表明 tet(Y)的起源来自气单胞菌。tet(Y)的过表达导致替加环素 MIC 增加 2 至 4 倍。电穿孔引入携带 tet(Y)的质粒 p2016GDAB1 导致替加环素 MIC 增加 16 倍,但不能通过接合转移到替加环素敏感的鲍曼不动杆菌受体中。携带 tet(Y)基因的分离株对替加环素压力敏感,对替加环素的敏感性降低。携带 tet(Y)的质粒在宿主菌株中稳定维持。
本研究在鲍曼不动杆菌中鉴定了替加环素耐药相关基因 tet(Y)。该基因赋予了增加的替加环素 MIC,可移动元件 Tn5393 可能在其在分离株之间的传播中发挥作用。