文献类型： 外文期刊

作者： Yang, Min ¹ ; Jia, Shi-Hua ² ; Tao, Hui-Ling ³ ; Zhu, Chen ² ; Jia, Wan-Zhong ⁴ ; Hu, Li-Hua ² ; Gao, Chun-Hui ⁵ ;

作者机构： 1.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China

2.Huazhong Agr Univ, Coll Life Sci & Technol, Wuhan 430070, Peoples R China

3.Yunnan Acad Agr Sci, Int Agr Inst, Kunming 650224, Yunnan, Peoples R China

4.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Vet Etiol Biol, Lanzhou 730046, Peoples R China

5.Huazhong Agr Univ, Coll Resources & Environm, Room 225,1 Shizishan Rd, Wuhan 430070, Peoples R China

关键词： ArsR; arsC; cdiR; drug susceptibility; transcriptional regulator

期刊名称：JOURNAL OF BIOCHEMISTRY （ 影响因子：3.387； 五年影响因子：3.169 ）

ISSN： 0021-924X

年卷期： 2021 年 169 卷 1 期

页码：

收录情况： SCI

摘要： It is urgent to understand the regulatory mechanism of drug resistance in widespread bacterial pathogens. In Mycobacterium tuberculosis, several transcriptional regulators have been found to play essential roles in regulating its drug resistance. In this study, we found that an ArsR family transcription regulator encoded by Rv2642 (CdiR) responds to isoniazid (INH), a widely used anti-tuberculosis (TB) drug. CdiR negatively regulates self and adjacent genes, including arsC (arsenie-transport integral membrane protein ArsC). CdiR directly interacts with INH and Cd(II). The binding of INH and Cd(II) both reduce its DNA-binding activity. Disrupting cdiR increased the drug susceptibility to INH, whereas overexpressing cdiR decreased the susceptibility. Strikingly, overexpressing arsC increased the drug susceptibility as well as cdiR. Additionally, both changes in cdiR and arsC expression caused sensitivity to other drugs such as rifamycin and ethambutol, where the minimal inhibitory concentrations in the cdiR deletion strain were equal to those of the arsC-overexpressing strain, suggesting that the function of CdiR in regulating drug resistance primarily depends on arsC. Furthermore, we found that Cd(II) enhances bacterial resistance to INH in a CdiR-dependent manner. As a conclusion, CdiR has a critical role in directing the interplay between Cd(II) metal ions and drug susceptibility in mycobacteria.