Regulation of the Bacillus subtilis fur and perR genes by PerR:: Not all members of the PerR regulon are peroxide inducible

Regulation of the Bacillus subtilis fur and perR genes by PerR:: Not all members of the PerR regulon are peroxide inducible
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DOI:
10.1128/jb.184.12.3276-3286.2002
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发表时间:
2002-06-01
影响因子:
3.2
通讯作者:
Helmann, JD
Helmann, JD
中科院分区:
生物学3区
文献类型:
--
作者:
Fuangthong, M;Herbig, AF;Helmann, JD

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PerR是一种铁摄取抑制蛋白(Fur)的同源物,在枯草芽孢杆菌中作为诱导性过氧化物应激反应的核心调节因子发挥作用。先前已证明PerR可调节mrgA、katA、ahpCF、hemAXCDBL和zosA基因。我们现在证明PerR还介导其自身基因以及fur基因的抑制。虽然PerR对大多数靶基因的抑制可由锰或铁引发,但对perR和fur的抑制对锰具有选择性。遗传学研究表明,锰或铁对PerR调节子基因的抑制需要PerR,且通常不依赖于Fur。实际上,在fur突变体中,铁介导的抑制作用增强。出乎意料的是,锰对fur基因的抑制似乎需要PerR和Fur两者,但只有PerR能与Nitro中的fur调控区结合。fur突变似乎通过影响细胞金属离子库间接起作用,从而影响PerR介导的抑制。虽然perR调节子的许多成分可被过氧化氢强烈诱导,但几乎无法证明fur和perR有任何诱导作用。因此,并非PerR调节子的所有成分都是过氧化物刺激子的成分。我们认为PerR以不同的金属化形式存在,这些形式在DNA靶标选择性和对氧化的敏感性方面存在差异。这一模型得到以下观察结果的支持:生长培养基的金属离子组成可极大地影响各种PerR调节子基因对过氧化氢的转录反应。
PerR is a ferric uptake repressor (Fur) homolog that functions as the central regulator of the inducible peroxide stress response in Bacillus subtilis. PerR has been previously demonstrated to regulate the mrgA, katA, ahpCF, hemAXCDBL, and zosA genes. We now demonstrate that PerR also mediates both the repression of its own gene and that of fur. Whereas PerR-mediated repression of most target genes can be elicited by either manganese or iron, repression of perR and fur is selective for manganese. Genetic studies indicate that repression of PerR regulon genes by either manganese or iron requires PerR and is generally independent of Fur. Indeed, in a fur mutant. iron-mediated repression is enhanced. Unexpectedly. repression of the fur gene by manganese appears to require both PerR and Fur, but only PerR binds to the fur regulatory region in Nitro. The fur mutation appears to act indirectly by affecting cellular metal ion pools and thereby, affecting PerR-mediated repression, While many, components of the perR regulon are strongly induced by hydrogen peroxide, little, if any, induction of fur and perR could be demonstrated. Thus, not all components of the PerR regulon are components of the peroxide stimulon. We suggest that PerR exists in distinct metallated forms that differ in DNA target selectivity and in sensitivity to oxidation. This model is supported by the observation that the metal ion composition of the growth medium can greatly influence the transcriptional response of the various PerR regulon genes to hydrogen peroxide.