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）的反应及其对抗生素耐药性的作用。我们正在利用基于基因组的研究信息来阐明与细胞壁损伤反应有关的信号通路。我们已经进行了双组分信号转导系统VraSR的研究，该系统在体内被证明对金黄色葡萄球菌对细胞壁损伤（应激）的反应至关重要，并参与对细胞壁抑制剂的抗性。VraSR系统由膜结合传感器蛋白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能够通过非分支机制快速转导并可靠地引发对细胞壁应激的反应。此外，我们正在了解VraR的全球基因调控机制，并揭示与细菌对细胞壁应激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应激的反应机制铺平了道路。

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.