State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, No. 1, Shizishan Street, Hongshan District, Wuhan, China.
The State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, No. 1, Xujiaping, Chengguan District, Chinese Academy of Agricultural Sciences, Lanzhou, China.
J Biochem. 2019 Sep 1;166(3):237-243. doi: 10.1093/jb/mvz030.
The ferric uptake regulator A (FurA) plays an essential role in responding to oxidative stress in mycobacteria. The genome of Mycobacterium smegmatis harbours three FurA orthologs; however, the potential cross-talk and contribution to drug resistance of different furA operon remain underdetermined. In this study, we characterized the cross-regulation and effect in drug resistance of these orthologs from M. smegmatis. Cross-binding of FurA protein to furA promoter was observed. The binding of FurA1 to furA3p and FurA2 to furA1p or furA3p is even more pronounced than their self-binding. The three FurA proteins are all functional at repressing the expression of the peroxidase enzyme katG1/katG2 in vivo. When overexpressing any of the furA orthologs in M. smegmatis, the bacteria become more resistant to isoniazid (INH). This pattern is consistent with that in Mycobacterium bovis. However, the knockdown of furA does not affect the INH sensitivity. This is the first report of cross-talk and contribution to drug resistance of all three furA orthologs in M. smegmatis.
铁摄取调节剂 A（FurA）在分枝杆菌应对氧化应激中发挥着重要作用。分枝杆菌耻垢亚种的基因组中包含三个 FurA 同源物；然而，不同 furA 操纵子之间的潜在串扰和对耐药性的贡献仍未确定。在这项研究中，我们对来自 M. smegmatis 的这些同源物的交叉调控和耐药性效应进行了表征。观察到 FurA 蛋白与 furA 启动子的交叉结合。FurA1 与 furA3p 的结合以及 FurA2 与 furA1p 或 furA3p 的结合比其自身结合更为明显。这三种 FurA 蛋白都能在体内抑制过氧化物酶 katG1/katG2 的表达。当在耻垢分枝杆菌中过表达任何一个 furA 同源物时，细菌对异烟肼（INH）的耐药性增强。这种模式与牛分枝杆菌一致。然而，furA 的敲低并不影响 INH 的敏感性。这是首次报道耻垢分枝杆菌中所有三个 furA 同源物之间的串扰和对耐药性的贡献。
