文献类型： 外文期刊

作者： Yang, Min ¹ ; Zhang, Li ¹ ; Tao, Hui-Ling ² ; Sun, Yuan-Chao ¹ ; Lou, Zhong-Zi ³ ; Jia, Wan-Zhong ³ ; Hu, Li-Hua ¹ ; Gao, ¹ ;

作者机构： 1.Huazhong Agr Univ, Coll Life Sci & Technol, State Key Lab Agr Microbiol, 1 Shizishan Rd, Wuhan 430070, Hubei, Peoples R China

2.Yunnan Acad Agr Sci, Int Agr Inst, 2338 Beijing China Rd, Kunming 650000, Yunnan, Peoples R China

3.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Vet Etiol Biol, 1 Xujiaping, Lanzhou 730046, Gansu, Peoples R China

4.Huazhong Agr Univ, Coll Resources & Environm, State Key Lab Agr Microbiol, 1 Shizishan Rd, Wuhan 430070, Hubei, Peoples R China

关键词： transcriptional regulation; isoniazid; drug resistance

期刊名称：FEMS MICROBIOLOGY LETTERS （ 影响因子：2.742； 五年影响因子：2.856 ）

ISSN： 0378-1097

年卷期： 2019 年 366 卷 10 期

页码：

收录情况： SCI

摘要： The bacteria drug resistance is not only associated with the gain of drug resistance gene but also relied on the adaptation of bacterial cells to antibiotics by transcriptional regulation. However, only a few transcription factors that regulate drug resistance have been characterized in mycobacteria. In this study, a TetR family transcriptional factor (OxiR), encoded by Rv0067c in Mycobacterium tuberculosis, was found to be an isoniazid (INH) resistance regulator. Comparing with the wild-type strain, the oxiR overexpressing strain is four times resistant to INH, whereas the oxiR knockout strain is eight times sensitive to INH. However, the rifamycin and ethambutol resistance were not influenced by oxiR. OxiR can bind to self-promoter at a 66 bp imperfect palindromic motifs. Interestingly, OxiR directly binds to INH, and thereby alleviate the self-repression. Furthermore, OxiR negatively regulated an oxidoreductase encoded by Rv0068. And the susceptibility of the Rv0068-overexpressing and oxiR knockout strains to all the three above-mentioned anti-tuberculosis drugs was equivalent, suggesting that the effect of oxiR to INH susceptibility is attributed to the derepression of Rv0068. In conclusion, we showed that OxiR can specifically modulate INH susceptibility by regulating an oxidoreductase encoding gene, both of which have not been associated with drug-resistance previously.