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

本实验室的研究重点是阐明和理解参与细菌防御机制的基因的生物学功能，以对抗抗菌剂对细胞壁肽聚糖造成的压力。面对医院和社区中越来越多的耐药细菌菌株，这些药物已经变得无效。我的实验室正在使用来自基因组研究的信息来阐明在细菌细胞壁被抑制时激活的信号通路。这一知识将对理解细菌如何在存在环境威胁的情况下进化，以及如何进一步利用这些机制在抗菌剂存在的情况下生存具有重要意义。我的研究计划的目标是：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)鉴定细胞壁损伤时引发的信号(S)。目前，我们已经证明了一种两组分的信号转导负责调节一种鲜为人知的蛋白质，我们已经证明这种蛋白质与肽聚糖和β-内酰胺类抗生素相互作用。我们正在解开其他与细菌对细胞壁活性抗生素的反应密切相关的基因的功能。拟议的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，这引起了参与日益增长的抗生素耐药性问题的研究界的极大兴趣。因为，它将为开发处理抗生素耐药性和治疗细菌感染的新策略提供见解。

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.