Novel tigecycline resistance mechanisms in Acinetobacter baumannii mediated by mutations in adeS, rpoB and rrf.
Novel tigecycline resistance mechanisms in Acinetobacter baumannii mediated by mutations in adeS, rpoB and rrf.
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由adeS、rpoB和rrf突变介导的鲍曼不动杆菌新的替加环素耐药机制
DOI：
10.1080/22221751.2021.1948804
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Hua X;He J;Wang J;Zhang L;Zhang L;Xu Q;Shi K;Leptihn S;Shi Y;Fu X;Zhu P;Higgins PG;Yu Y
鲍曼不动杆菌是医院获得性感染的重要病原菌。尽管替加环素目前仍是治疗多药耐药A.鲍曼不动杆菌（MDRAB）菌株，替加环素耐药分离株的报告大幅增加。对替加环素的耐药机制进行了研究。鲍曼不动杆菌比迄今为止文献中所描述的要复杂和多样得多。在这里，我们的特点是在体外选择的MDRAB菌株通过增加浓度的替加环素。我们已经确定了导致替加环素敏感性降低的adeS、rrf和rpoB的艾德突变。使用原位互补实验，我们证实rrf，rpoB突变和两种类型得adeS突变与替加环素耐药相关.通过Western blot和多聚体分析，我们证实rrf突变导致RRF表达降低，进而影响核糖体循环过程，最终导致替加环素耐受性增加。转录分析显示，突变的rpoB基因在调节SAM依赖性甲基转移酶（trm）和转录调节因子的表达中起作用，从而产生中度替加环素耐药性。本研究提供了直接的体外证据，即adeS、rpoB和rrf突变与A.鲍曼不动杆菌。
ABSTRACT Acinetobacter baumannii is an important pathogen in hospital acquired infections. Although tigecycline currently remains a potent antibiotic for treating infections caused by multidrug resistant A. baumannii (MDRAB) strains, reports of tigecycline resistant isolates have substantially increased. The resistance mechanisms to tigecycline in A. baumannii are far more complicated and diverse than what has been described in the literature so far. Here, we characterize in vitro-selected MDRAB strains obtained by increasing concentrations of tigecycline. We have identified mutations in adeS, rrf and rpoB that result in reduced susceptibility to tigecycline. Using in situ complementation experiments, we confirm that mutations in rrf, rpoB, and two types of mutations in adeS correlate with tigecycline resistance. By Western blot and polysome profile analysis, we demonstrate that the rrf mutation results in decreased expression of RRF, which affects the process of ribosome recycling ultimately leading to increased tigecycline tolerance. A transcriptional analysis shows that the mutated rpoB gene plays a role in regulating the expression of the SAM-dependent methyltransferase (trm) and transcriptional regulators, to confer moderate tigecycline resistance. This study provides direct in vitro evidence that mutations in the adeS, rpoB and rrf are associated with tigecycline resistance in A. baumannii.
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影响因子：
5.7
作者：
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