Anti-HIV agent azidothymidine decreases Tet(X)-mediated bacterial resistance to tigecycline in Escherichia coli
Anti-HIV agent azidothymidine decreases Tet(X)-mediated bacterial resistance to tigecycline in Escherichia coli
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DOI：
10.1038/s42003-020-0877-5
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发表时间：
2020-04-03
影响因子：
5.9
通讯作者：
Wang, Zhiqiang
中科院分区：
文献类型：
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作者：
Liu, Yuan;Jia, Yuqian;Wang, Zhiqiang
Yuan Liu等人。证明抗HIV剂氮噻嗪胺可恢复替甘克林对这种抗生素抗性的病原体的活性。这项研究表明，叠氮甲噻嗪和Tigecycline是一种有效的方案，可以治疗由耐足菌线引起的感染。耐铁甲基抗性的大肠杆菌的出现。高级tigecycycline的出现，由TET（X3/X4）在肠car虫中介导的高水平Tigevecyclies抗药性，以构成TEST（X3/X4）的构成。全世界。抗生素辅助策略通过干扰固有抗性机制或增强抗生素作用，使抗生素对这些抗性病原体有效。在本文中，我们筛选了一系列药物，以识别能够恢复针对抗性病原体的Tigecycline活性的化合物。令人鼓舞的是，我们发现抗HIV剂氮噻嗪胺显着增强了针对临床抗性细菌的Tigecycline活性。同时，偶氮苷的添加阻止了大肠杆菌中的替物林抗性和TET自然存在的水平转移（X4）。证据表明，叠氮噻嗪明确抑制了DNA合成并抑制抗性酶活性。此外，在TET（X4）表达大肠杆菌的体内感染模型中，叠氮噻噻替胺和Tigecycline的组合具有显着的治疗益处，包括增加存活率和减轻细菌负担。这些发现提供了一种有效的方案，可以治疗由抗替克林抗性大肠杆菌引起的感染。
Yuan Liu et al. demonstrate that anti-HIV agent azidothymidine restores tigecycline's activity against pathogens resistant to this antibiotic. This study suggests the combination of azidothymidine and tigecycline as an effective regimen to treat infections caused by tigecycline-resistant Escherichia coli.Recent emergence of high-level tigecycline resistance mediated by Tet(X3/X4) in Enterobacteriaceae undoubtably constitutes a serious threat for public health worldwide. Antibiotic adjuvant strategy makes antibiotic more effective against these resistant pathogens through interfering intrinsic resistance mechanisms or enhancing antibiotic actions. Herein, we screened a collection of drugs to identify compounds that are able to restore tigecycline activity against resistant pathogens. Encouragingly, we discovered that anti-HIV agent azidothymidine dramatically potentiates tigecycline activity against clinically resistant bacteria. Meanwhile, addition of azidothymidine prevents the evolution of tigecycline resistance in E. coli and the naturally occurring horizontal transfer of tet(X4). Evidence demonstrated that azidothymidine specifically inhibits DNA synthesis and suppresses resistance enzyme activity. Moreover, in in vivo infection models by Tet(X4)-expression E. coli, the combination of azidothymidine and tigecycline achieved remarkable treatment benefits including increased survival and decreased bacterial burden. These findings provide an effective regimen to treat infections caused by tigecycline-resistant Escherichia coli.