AbfR调控表皮葡萄球菌生物膜形成的分子机制研究

项目名称： AbfR调控表皮葡萄球菌生物膜形成的分子机制研究

项目编号： No.31500110

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 刘幸

作者单位： 中国科学院上海药物研究所

项目金额： 21万元

中文摘要： 表皮葡萄球菌（简称表葡菌）是一种在人体皮肤和粘膜表面广泛存在的凝固酶阴性的条件致病性菌。随着各类植入性材料在临床上的广泛应用，表葡菌已经成为引起医院内感染的前四位病原体之一，因其生物膜的保护作用，易发生多重耐药难以治疗，最终导致医疗材料植入的失败，造成巨大的经济损失。. 前期工作中，我们鉴定了表葡菌中一个全新的与多重耐药性相关的转录因子AbfR。研究发现AbfR缺失能影响生物膜的形成从而使表葡菌丧失耐药性，因此AbfR很可能成为一个新型抗菌药物靶标，但是AbfR影响生物膜形成的分子机制仍有待进一步研究，这对开发积极有效的抗菌药物十分关键。. 本项目拟综合蛋白质组学、分子生物学、病原细菌学等多种学科手段深入研究转录因子AbfR影响表葡菌生物膜形成的相关信号通路及其基于活性半胱氨酸的磷酸化的转录调控机制，更加详尽地了解这一潜在的新型抗菌靶标，进而为小分子抑制剂的特异性筛选提供理论依据。

中文关键词： 生物膜；转录因子；多重耐药性；表皮葡萄球菌；非标记定量蛋白质组学

英文摘要： Staphylococcus epidermidis is a coagulase-negative and opportunistic pathogen, which normally inhabits human skin and mucous membranes. Along with indwelling medical devices are performed on patients, S.epidermidis ranks fourth among the most important nosocomial pathogens. The protective effect of biofilm in S.epidermidis increased multi-antibiotics resistance, and ultimately lead to the failure of implanted medical devices. Consequently, S. epidermidis infection has become a widespread troublesome problem as they are extremely difficult to treat, and represents a serious burden for the public health system..In our previous work , We identified the first oxidation-sensing regulator AbfR in S.epidermidis.Our results demonstrated that AbfR is involved in biofilm formation, evidenced by the loss of antibiotic resistance of S.epidermidis in the abfR mutant. Therefore, AbfR is likely to be applied as a new antibacterial drug target. To achieve this, it is necessary to decipher the molecular mechanism of AbfR regulating biofilm formation..We are motivated to integrate multiple methods of proteomics, molecular biology and microbiology to evaluate signaling pathways of biofilm formation which affected by AbfR, and to decode the regulation mechanism of cysteine phosphorylation of AbfR. This project will deepen the understanding of the potential novel antibacterial target, thus providing theoretical basis for the specificity screening of small molecule inhibitors used for the design of antibacterial drug.

英文关键词： biofilm;transcription factor;multi-antibiotics resistance; Staphylococcus epidermidis ;label-free quantitative proteomics