Elucidation of the molecular mechanism of S. aureus response to cell wall damage

我实验室的研究重点是了解金黄色葡萄球菌对靶向细胞壁生物合成的抗菌剂--即细胞壁抑制剂--的反应，以及它对抗生素耐药性的作用。我们正在使用来自基因组研究的信息来阐明与细胞壁损伤反应有关的信号通路。我们已经开展了一个双组分信号转导系统VraSR的研究，该系统在体内被证明是金黄色葡萄球菌对细胞壁损伤(胁迫)的反应所必需的，并参与了对细胞壁抑制剂的抗性。VraSR系统由膜结合的传感蛋白VraS、组氨酸激酶和细胞质反应调节蛋白Vrar、转录因子组成。我们的初步研究表明，VraSR能够通过一种非分枝机制快速传递并可靠地引发对细胞壁压力的反应。此外，我们正在了解Vrar的全球基因调控机制，并解开与细菌对细胞壁压力的反应有关的基因的功能。以上研究为深入研究金黄色葡萄球菌对细胞壁胁迫的反应机制奠定了基础。

Research in my laboratory is focused on understanding the Staphylococcus aureus response to antibacterial agents that target cell wall biosynthesis, namely cell wall inhibitors, and its role to antibiotic resistance. We are using information from genome-based research to elucidate the signaling pathways involved with cell wall damage response. We have undertaken the study of a two-component signal transduction system, VraSR, which was shown in vivo to be essential to the S. aureus response against cell wall damage (stress) and to be involved in resistance to cell wall inhibitors. The VraSR system is composed of a membrane bound sensor protein, VraS, a histidine kinase, and a cytoplasmic response regulatory protein VraR, a transcription factor. Our initial studies indicate that VraSR is capable of rapidly transducing and reliably eliciting a response to cell wall stress via a non-branched mechanism. Further, we are in the process of understanding the global gene-regulatory mechanism of VraR and unraveling the functions of genes that are involved with the bacterial response to cell wall stress. The above studies have paved the road for an in depth research of the mechanism of S. aureus response to cell wall stress.