Staphylococcus aureus ArcR controls expression of the arginine deiminase operon
Staphylococcus aureus ArcR controls expression of the arginine deiminase operon
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DOI：
10.1128/jb.00592-07
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发表时间：
2007-08-01
影响因子：
3.2
通讯作者：
Aharonowitz, Yair
中科院分区：
文献类型：
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作者：
Makhlin, Julia;Kofman, Tzili;Aharonowitz, Yair
我们在所有测序的金黄色葡萄球菌基因组中鉴定了一个与ArcR（细菌转录调节因子的Crp/Fnr家族成员）非常相似的单一开放阅读框架。编码ArcR的arcR基因与精氨酸脱亚胺酶（ADI）途径基因arcABDC形成操纵子，其使得能够利用精氨酸作为厌氧条件下生长的能量来源。在这份报告中，我们表明，在厌氧条件下，S。金黄色葡萄球菌的生长受到葡萄糖分解代谢抑制，并被精氨酸增强。同样，葡萄糖和精氨酸对arcABDCR基因的转录具有相互作用。此外，我们使用的突变体删除arcR的弧操纵子在厌氧条件下的转录严格依赖于一个功能性的arcR。这些发现得到了蛋白质组分析的支持，蛋白质组分析表明，在厌氧条件下，ADI分解代谢蛋白的表达依赖于ArcR。生物信息学分析S. aureus ArcR预测了N-末端核苷酸结合结构域和C-末端螺旋-转角-螺旋DNA结合基序。ArcR与存在于arc启动子区的保守的CRP样序列基序TGTGA-N-6-TCACA结合，从而激活ADI途径基因的表达。在其他30种S.金黄色葡萄球菌基因主要编码厌氧酶系统、毒力因子和调节系统。对ArcR进行了测试，发现其与adh 1、lctE、srrAB和lukM四种基因的调控区结合。在一种情况下，对于编码L-乳酸脱氢酶的lctE，ArcR仅能够在环AMP存在下结合。这些观察结果表明，ArcR可能在厌氧生长所需的许多基因的表达中发挥重要作用。
We identified a single open reading frame that is strongly similar to ArcR, a member of the Crp/Fnr family of bacterial transcriptional regulators, in all sequenced Staphylococcus aureus genomes. The arcR gene encoding ArcR forms an operon with the arginine deiminase (ADI) pathway genes arcABDC that enable the utilization of arginine as a source of energy for growth under anaerobic conditions. In this report, we show that under anaerobic conditions, S. aureus growth is subject to glucose catabolic repression and is enhanced by arginine. Likewise, glucose and arginine have reciprocal effects on the transcription of the arcABDCR genes. Furthermore, we show using a mutant deleted for arcR that the transcription of the arc operon under anaerobic conditions depends strictly on a functional ArcR. These findings are supported by proteome analyses, which showed that under anaerobic conditions the expression of the ADI catabolic proteins depends on ArcR. Bioinformatic analysis of S. aureus ArcR predicts an N-terminal nucleotide binding domain and a C-terminal helix-turn-helix DNA binding motif. ArcR binds to a conserved Crp-like sequence motif, TGTGA-N-6-TCACA, present in the arc promoter region and thereby activates the expression of the ADI pathway genes. Crp-like sequence motifs were also found in the regulatory regions of some 30 other S. aureus genes mostly encoding anaerobic enzymatic systems, virulence factors, and regulatory systems. ArcR was tested and found to bind to the regulatory regions of four such genes, adh1, lctE, srrAB, and lukM. In one case, for lctE, encoding L-lactate dehydrogenase, ArcR was able to bind only in the presence of cyclic AMP. These observations suggest that ArcR is likely to play an important role in the expression of numerous genes required for anaerobic growth.