Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor
Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor
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DOI：
10.1186/1471-2164-9-607
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发表时间：
2008-12-16
期刊：
影响因子：
4.4
通讯作者：
Shelver, Daniel
中科院分区：
文献类型：
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作者：
Bryan, Joshua D.;Liles, Roxanne;Shelver, Daniel
背景：无乳链球菌（B组链球菌; GBS）是新生儿的重要病原菌，也是成人的新兴病原菌。虽然转录调节因子在GBS基因组中大量编码，但它们在GBS发病机制中的作用知之甚少。mtaR基因编码一个推定的LysR型转录调节因子，该因子对GBS的完全毒力至关重要。先前的研究表明，mtaR突变体以降低的速率转运甲硫氨酸，并且在未补充甲硫氨酸的正常人血浆中生长不良。MTAR突变体的毒性降低与甲硫氨酸转运缺陷相关;然而，没有MTAR调节基因被identified.Results：野生型GBS和MTAR突变体的微阵列分析显示12个基因的差异表达，包括1个上调和11个下调基因的MTAR突变体。在下调的基因中，我们确定了一组共转录的基因，编码一个假定的蛋氨酸转运蛋白（metQ INP）和肽酶（胰M）。可能参与精氨酸转运（artPQ）和精氨酸生物合成（argGH）的四个基因的表达下调，这些基因定位于两个转录单位。编码细胞外蛋白酶的毒力因子cspA被下调。此外，SAN_1255位点，其中puplatin编码的蛋白质显示相似的纤溶酶原激活剂，是downregulated.Conclusion：据我们所知，这是第一个研究，以描述全球影响MtaR GBS基因的表达。这项研究暗示metQINP基因编码的MtaR调节的蛋氨酸转运蛋白，这可能提供了一个机制的解释蛋氨酸依赖的生长缺陷的mtaR突变体。除了调节参与代谢和氨基酸转运的基因的表达外，mtaR的失活还影响了与发病机制有关的其他GBS基因的表达。这些发现表明MtaR可能通过调节许多基因的表达在GBS发病机制中发挥多方面的作用。
Background: Streptococcus agalactiae ( group B Streptococcus; GBS) is a significant bacterial pathogen of neonates and an emerging pathogen of adults. Though transcriptional regulators are abundantly encoded on the GBS genome, their role in GBS pathogenesis is poorly understood. The mtaR gene encodes a putative LysR-type transcriptional regulator that is critical for the full virulence of GBS. Previous studies have shown that an mtaR-mutant transports methionine at reduced rates and grows poorly in normal human plasma not supplemented with methionine. The decreased virulence of the mtaR mutant was correlated with a methionine transport defect; however, no MtaR-regulated genes were identified.Results: Microarray analysis of wild-type GBS and an mtaR mutant revealed differential expression of 12 genes, including 1 upregulated and 11 downregulated genes in the mtaR mutant. Among the downregulated genes, we identified a cluster of cotranscribed genes encoding a putative methionine transporter (metQ INP) and peptidase (pdsM). The expression of four genes potentially involved in arginine transport (artPQ) and arginine biosynthesis (argGH) was downregulated and these genes localized to two transcriptional units. The virulence factor cspA, which encodes an extracellular protease, was downregulated. Additionally, the SAN_1255 locus, which putatively encodes a protein displaying similarity to plasminogen activators, was downregulated.Conclusion: To our knowledge, this is the first study to describe the global influence of MtaR on GBS gene expression. This study implicates the metQINP genes as encoding the MtaR-regulated methionine transporter, which may provide a mechanistic explanation for the methionine-dependent growth defect of the mtaR mutant. In addition to modulating the expression of genes involved in metabolism and amino acid transport, inactivation of mtaR affected the expression of other GBS genes implicated in pathogenesis. These findings suggest the possibility that MtaR may play a multifaceted role in GBS pathogenesis by regulating the expression of numerous genes.