MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake
MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake
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DOI：
10.1046/j.1365-2958.2002.02944.x
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发表时间：
2002-06-01
影响因子：
3.6
通讯作者：
Foster, SJ
中科院分区：
文献类型：
--
作者：
Horsburgh, MJ;Wharton, SJ;Foster, SJ
金黄色葡萄球菌类DtxR蛋白MntR控制编码假定的锰转运蛋白的mntABC和mntH基因的表达。mntABC的突变在金属缺乏的培养基中产生生长缺陷，并增加了对细胞内产生的超氧自由基的敏感性。这些表型是由于锰摄取减少所致，并且通过添加过量的Mn(II)得以挽救。对于STE035（mntA mntH），Mn(II)对超氧化物抗性的挽救不完全，并且该菌株在小鼠脓肿感染模型中的毒力降低。mntABC的表达以依赖MntR的方式被Mn(II)抑制，这与mntH的表达形成对比，mntH在高Mn(II)环境中不受抑制，并且在mntR突变体中表达降低。这表明MntR分别作为这些基因座的负向和正向调节因子。PerR是过氧化物抗性调节子阻遏物，与MntR共同控制mntABC的表达和锰的摄取。当在过量Mn(II)中生长时，STE031（mntR）中PerR调节的基因katA（过氧化氢酶）、ftn（铁蛋白）和fur（铁摄取调节因子）的表达降低。因此，MntR通过控制Mn(II)的摄取来调节PerR调节子中受Mn(II)调节的成员以及Fur蛋白。讨论了金黄色葡萄球菌通过调节因子MntR、PerR和Fur对金属离子内稳态和抗氧化应激的协同调节。
The Staphylococcus aureus DtxR-like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal-depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH ), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR-dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci re-spectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR-regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR ) when grown in excess Mn(II). Therefore, the control of Mn(II)-regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co-ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.