CymR, the master regulator of cysteine metabolism in Staphylococcus aureus, controls host sulphur source utilization and plays a role in biofilm formation
CymR, the master regulator of cysteine metabolism in Staphylococcus aureus, controls host sulphur source utilization and plays a role in biofilm formation
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DOI：
10.1111/j.1365-2958.2009.06760.x
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发表时间：
2009-07-01
影响因子：
3.6
通讯作者：
Martin-Verstraete, Isabelle
中科院分区：
文献类型：
--
作者：
Soutourina, Olga;Poupel, Olivier;Martin-Verstraete, Isabelle
我们已经确定了金黄色葡萄球菌中半胱氨酸代谢的主要调节因子CymR的特征。CymR抑制参与导致半胱氨酸形成的途径的基因的转录。八个直接的DNA目标，确定使用凝胶移位或足迹实验。比较转录组分析和体外研究表明，CysM，OAS-巯基裂解酶，也牵连在这个调控系统。半胱氨酸的直接前体OAS阻止CymR依赖性结合DNA。这项研究使我们能够预测硫代谢功能，以前未知的S。aureus基因。我们证明了S.金黄色葡萄球菌能够在作为唯一硫源的高半胱氨酸上生长，表明该化合物有效地MccA和MccB依赖性转化为半胱氨酸。我们认为SA 1850是一种新的硫代硫酸盐转运蛋白，TcyP和TcyABC是L-胱氨酸转运蛋白。CymR直接控制人类来源的硫源如牛磺酸和同型半胱氨酸的使用。cymR突变体也显示出形成生物膜的能力降低，表明CymR参与了S.金黄色葡萄球菌通过独立于ICA的机制。这些数据表明，微调硫代谢起着重要的作用，在这一主要病原体的生理和适应环境条件和生存的主机。
We have characterized the master regulator of cysteine metabolism, CymR, in Staphylococcus aureus. CymR repressed the transcription of genes involved in pathways leading to cysteine formation. Eight direct DNA targets were identified using gel-shift or footprinting experiments. Comparative transcriptome analysis and in vitro studies indicated that CysM, the OAS-thiol-lyase, was also implicated in this regulatory system. OAS, the direct precursor of cysteine, prevents CymR-dependent binding to DNA. This study has allowed us to predict sulphur metabolism functions for previously uncharacterized S. aureus genes. We show that S. aureus is able to grow on homocysteine as the sole sulphur source suggesting efficient MccA and MccB-dependent conversion of this compound into cysteine. We propose that SA1850 is a new thiosulphate transporter and that TcyP and TcyABC are L-cystine transporters. CymR directly controls the use of sulphur sources of human origin such as taurine and homocysteine. The cymR mutant also displayed a reduced capacity to form biofilms, indicating that CymR is involved in controlling this process in S. aureus via an ica-independent mechanism. These data indicate that fine-tuning of sulphur metabolism plays an important part in the physiology of this major pathogen and its adaptation to environmental conditions and survival in the host.