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首页> 外文期刊>Infection and immunity >Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence
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Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence

机译：MTSR的表征，一种新的金属调节剂，在一组链球菌中，涉及铁采集和毒力

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Group A streptococcus (GAS) is a common pathogen of the human skin and mucosal surfaces capable of producing a variety of diseases. In this study, we investigated regulation of iron uptake in GAS and the role of a putative transcriptional regulator named MtsR (for Mts repressor) with homology to the DtxR family of metal-dependent regulatory proteins. An mtsR mutant was constructed in NZ131 (M49 serotype) and analyzed. Western blot and RNA analysis showed that mtsR inactivation results in constitutive transcription of the sia (streptococcal iron acquisition) operon, which was negatively regulated by iron in the parent strain. A recombinant MtsR with C-terminal His6 tag fusion (rMtsR) was cloned and purified. Electrophoretic mobility gel shift assays demonstrated that rMtsR specifically binds to the sia promoter region in an iron- and manganese-dependent manner. Together, these observations indicate that MtsR directly represses the sia operon during cell growth under conditions of high metal levels. Consistent with deregulation of iron uptake, the mtsR mutant is hypersensitive to streptonigrin and hydrogen peroxide, and 55Fe uptake assays demonstrate that it accumulates 80% ± 22.5% more iron than the wild-type strain during growth in complete medium. Studies with a zebrafish infection model revealed that the mtsR mutant is attenuated for virulence in both the intramuscular and the intraperitoneal routes. In conclusion, MtsR, a new regulatory protein in GAS, controls iron homeostasis and has a role in disease production.
机译：组链球菌（气体）是能够产生各种疾病的人体皮肤和粘膜表面的常见病原体。在这项研究中，我们调查了对气体的铁吸收的调节以及调用转录调节因子的作用，该调节调节因子与MTSR（MTS阻遏物）的依赖于DTXR家族的依赖性调节蛋白的同源性。在NZ131（M49血清型）中构建了 MTSR 突变体并分析。 Western印迹和RNA分析表明， MTSR 灭活导致 SIA （链球菌铁采集）操纵子的组成型转录，其通过母体菌株中的铁负调节。克隆并纯化具有C-末端的重组MTSR His 6 标签融合（RMTSR）。电泳迁移型凝胶移位测定证明RMTSR以铁和载锰依赖性方式特异性结合到 Sia 启动子区。这些观察结果表明，在高金属水平条件下，MTSR直接在细胞生长期间抑制 SIA 操纵子。符合熨斗吸收的放入压制， MTSR 突变体对斯特勒塞尔蛋白和过氧化氢过敏， 55 Fe摄取测定表明它比熨斗更加80％±22.5％完全培养基生长期间的野生型菌株。用斑马鱼感染模型的研究表明，肌肉内和腹膜内途径中的毒力衰减 MTSR 突变体。总之，MTSR是一种新的气体调节蛋白，对抗铁袜，并在疾病生产中作用。

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