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

本实验室的研究主要集中在阐明和理解细菌防御机制相关基因的生物学功能，以对抗抗菌剂对细胞壁肽聚糖造成的应激。面对医院环境和社区中越来越多的耐药菌株，这些药物已变得无效。 我的实验室正在使用基于基因组的研究信息来阐明抑制细菌细胞壁后激活的信号通路。这些知识对于理解细菌如何在环境威胁的存在下进化以及这些机制如何在抗菌剂的存在下进一步用于生存具有重要意义。 我的研究项目的目标是：1）阐明金黄色葡萄球菌对抑制肽聚糖生物合成的抗菌剂反应的分子机制; 2）鉴定细胞壁损伤后引起的信号。 目前，我们已经证明，一个双组分信号转导是负责一个鲜为人知的蛋白质，我们已经证明，与肽聚糖和β-内酰胺抗生素相互作用的调节。我们正在解开与细菌对细胞壁活性抗生素的反应密切相关的其他基因的功能。本研究为进一步研究S.金黄色葡萄球菌，这是非常感兴趣的研究社区参与日益增加的问题，抗生素耐药性。 因为，它将为应对抗生素耐药性和治疗细菌感染的新策略的发展提供见解。

Research in my laboratory is focused on elucidating and understanding the biological function of genes involved with bacterial defense mechanism against stress caused to cell-wall peptidoglycan by antimicrobial agents. These agents have become in-effective in the face of ever increasing number of resistant bacterial strains in hospital settings and community.  My laboratory is using the information from the genome-based research to elucidate the signaling pathways that are activated upon the inhibition of the bacterial cell wall. This knowledge will be of a great importance in understanding how bacteria evolve in the presence of environmental threats and how these mechanisms are further used for survival in the presence of antibacterial agents.  The goals of my research program are: 1) elucidation of the molecular mechanisms that underline the Staphyloccocus aureus response to antimicrobial agents that inhibit peptidoglycan biosynthesis; and  2) Identification of the signal(s) elicited upon cell-wall damage.  At the moment we have demonstrated that a two-component signal transduction is responsible for the regulation of a little known protein that we have shown to interact with peptidoglycan and beta-lactam antibiotics. We are in the process on unraveling the function of other genes closely related with the bacterial response to cell-wall-active antibiotics. The proposed program constitutes a basic research on gene function and gene regulation in S. aureus that is of great interest to the research community involved with the ever increasing issue of antibiotic resistance.  For, it will provide insights on development of new strategies in dealing with antibiotic resistance and treating bacterial infections.