Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, People's Republic of China.
Emerg Microbes Infect. 2021 Dec;10(1):1404-1417. doi: 10.1080/22221751.2021.1948804.
is an important pathogen in hospital acquired infections. Although tigecycline currently remains a potent antibiotic for treating infections caused by multidrug resistant (MDRAB) strains, reports of tigecycline resistant isolates have substantially increased. The resistance mechanisms to tigecycline in are far more complicated and diverse than what has been described in the literature so far. Here, we characterize -selected MDRAB strains obtained by increasing concentrations of tigecycline. We have identified mutations in , and that result in reduced susceptibility to tigecycline. Using complementation experiments, we confirm that mutations in , , and two types of mutations in correlate with tigecycline resistance. By Western blot and polysome profile analysis, we demonstrate that the 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 gene plays a role in regulating the expression of the SAM-dependent methyltransferase () and transcriptional regulators, to confer moderate tigecycline resistance. This study provides direct evidence that mutations in the , and are associated with tigecycline resistance in .
是医院获得性感染的重要病原体。虽然替加环素目前仍然是治疗多药耐药 （MDRAB） 菌株引起感染的有效抗生素，但替加环素耐药分离株的报告显著增加。目前， 对替加环素的耐药机制远比文献中描述的更为复杂多样。在这里，我们通过增加替加环素浓度来选择 MDRAB 菌株。我们已经确定了导致对替加环素敏感性降低的 、 和 突变。通过 互补实验，我们证实了 、 和 中的两种突变与替加环素耐药相关。通过 Western blot 和多核糖体谱分析，我们证明了 突变导致 RRF 表达减少，这影响核糖体回收过程，最终导致对替加环素的耐受性增加。转录分析表明，突变的 基因在调节 SAM 依赖性甲基转移酶（）和转录调节因子的表达中起作用，从而赋予中度替加环素耐药性。这项研究提供了直接的证据，证明 、 和 中的突变与 对替加环素的耐药性有关。
