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Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria 期刊论文

编号：

840880e3-5eae-4153-b5ff-c21005eb8fad
作者：

Fan, XiaoYong(范小勇)^[1,2]Tang, BiKui^[3];Xu, YuanYuan^[1,4];Han, AngXuan^[1];Shi, KunXiong^[1];Wu, YongKai^[4];Ye, Yu^[5];Wei, Meili^[3];Niu, Chen(牛辰)^[1]Wong, KaWing^[1,2];Zhao, GuoPing^[4,5,6,7,8];Lyu, LiangDong^[1];
语种：

English
期刊：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ISSN：0027-8424 2018 年 115 卷 9 期 (2210 - 2215) ; FEB 27
收录：
关键词：

DNA double-strand breaks 5-OH-dCTP reactive oxygen species antibiotic Mycobacterium
摘要：

Growing evidence shows that generation of reactive oxygen species (ROS) derived from antibiotic-induced metabolic perturbation contribute to antibiotic lethality. However, our knowledge of the mechanisms by which antibiotic-induced oxidative stress actually kills cells remains elusive. Here, we show that oxidation of dCTP underlies ROS-mediated antibiotic lethality via induction of DNA double-strand breaks (DSBs). Deletion of mazG-encoded 5-OH-dCTP-specific pyrophosphohydrolase potentiates antibiotic killing of stationary-phase mycobacteria, but did not affect antibiotic efficacy in exponentially growing cultures. Critically, the effect of mazG deletion on potentiating antibiotic killing is associated with antibiotic-induced ROS and accumulation of 5-OH-dCTP. Independent lines of evidence presented here indicate that the increased level of DSBs observed in the Delta mazG mutant is a dead-end event accounting for enhanced antibiotic killing. Moreover, we provided genetic evidence that 5-OH-dCTP is incorporated into genomic DNA via error-prone DNA polymerase DnaE2 and repair of 5-OH-dC lesions via the endonuclease Nth leads to the generation of lethal DSBs. This work provides a mechanistic view of ROS-mediated antibiotic lethality in stationary phase and may have broad implications not only with respect to antibiotic lethality but also to the mechanism of stress-induced mutagenesis in bacteria.
推荐引用方式
GB/T 7714：

Fan Xiao-Yong,Tang Bi-Kui,Xu Yuan-Yuan, et al. Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria [J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2018,115(9):2210-2215.
APA：

Fan Xiao-Yong,Tang Bi-Kui,Xu Yuan-Yuan,Han Ang-Xuan,&Lyu Liang-Dong.(2018).Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,115(9):2210-2215.
MLA：

Fan Xiao-Yong, et al. "Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria" .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115,9(2018):2210-2215.

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