Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog
Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog
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DOI：
10.1128/iai.00435-10
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发表时间：
2010-11-01
影响因子：
3.1
通讯作者：
Adler, Ben
中科院分区：
文献类型：
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作者：
Lo, Miranda;Murray, Gerald L.;Adler, Ben
钩端螺旋体病是由钩端螺旋体属引起的一种全球性的人畜共患病。铁是大多数细菌生长所必需的。由于宿主体内铁的利用率低，病原体已经进化出复杂的铁获取机制来生存和建立感染。在许多细菌中，铁吸收和储存蛋白的表达受Fur调控。L.问号编码四个预测的毛皮同源物，我们已经构建了一个突变，其中之一，la1857。我们进行微阵列分析，以确定铁响应基因，并研究la1857突变对基因表达的影响。在铁限制条件下，野生型中有43个基因上调，49个基因下调。预测参与无机离子转运和代谢（包括TonB依赖性蛋白和外膜转运蛋白）的编码蛋白的基因在上调的列表中被过度表达，而54%的差异表达基因没有已知的功能。有16个功能未知的上调基因是在甜菊中缺失的。biflexa，并因此可以编码与遗传相关的因子。铁响应基因的表达没有显着影响的诱变LA 1857，表明LA 1857不是一个全球性的调节铁稳态。血红素生物合成基因和一个假定的过氧化氢酶的突变体的上调表明，LA1857是更相似的PerR，氧化应激反应的调节器。事实上，la1857突变体比野生型更能抵抗过氧化物胁迫。我们的研究结果提供了深入了解铁在钩端螺旋体代谢和氧化应激反应的调节中的作用，包括可能对毒力很重要的基因。
Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.