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

我实验室的研究重点是阐明和理解细菌防御机制中涉及的基因的生物学功能，以抵抗抗菌剂对细胞壁肽聚糖的应激。面对医院环境和社区中越来越多的耐药细菌菌株，这些药物已变得无效。我的实验室正在利用基因组研究的信息来阐明抑制细菌细胞壁时激活的信号通路。这些知识对于理解细菌在环境威胁下如何进化以及这些机制如何在抗菌剂存在下进一步用于生存具有重要意义。我的研究计划的目标是：1)阐明强调金黄色葡萄球菌对抑制肽聚糖生物合成的抗菌药物反应的分子机制；2)细胞壁损伤引起的信号识别。目前，我们已经证明了一种双组分信号转导负责调节一种鲜为人知的蛋白质，我们已经证明了这种蛋白质与肽聚糖和β -内酰胺抗生素相互作用。我们正在揭开与细菌对细胞壁活性抗生素反应密切相关的其他基因的功能。该计划构成了金黄色葡萄球菌基因功能和基因调控的基础研究，这是研究界对日益增加的抗生素耐药性问题非常感兴趣的。因为，它将为开发新的抗生素耐药性和治疗细菌感染的策略提供见解。

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.