噬菌体裂解酶细胞壁结合域抑制金黄色葡萄球菌生物膜形成的机理与应用

由于耐甲氧西林金黄色葡萄球菌（MRSA）对多种常用抗菌药物耐药，MRSA已成为全球公共卫生体系的重大危害。更为严重的是金黄色葡萄球菌还能以生物膜形式感染，导致更强的耐药性。因此，研究控制金黄色葡萄球菌生物膜形成的机理和方法有着重要的理论和实际意义。我们的前期研究发现噬菌体裂解酶细胞壁结合域（Cell wall binding domain, CBD）能以较高的亲和力特异性结合靶细菌，且单个靶细菌表面存在大量的CBD结合位点（约10的7次方个），是一种用于细菌表面修饰和改性的工具。考虑到表面粘附在生物膜形成过程中起的重要作用，本研究拟以金黄色葡萄球菌噬菌体裂解酶CBD为修饰工具，将其与不同电荷的蛋白质、群体感应抑制分子融合表达，研究改变金黄色葡萄球菌表面电荷和群体感应信号对其生物膜形成的影响，探索抑制金黄色葡萄球菌生物膜形成的新方法和途径，为金黄色葡萄球菌生物膜感染的控制提供新的解决思路。

Because of its multi-drug resistance, methicillin-resistant Staphylococcus aureus (MRSA) has become a global threat. Much worse, S. aureus could infect humans in the form of biofilm, which can lead to much stronger antimicrobial resistance. Therefore, it is important to find methods to inhibit its biofilm formation. In our previous research, we found that the cell wall binding domains (CBD) of bacteriophage lysins could be good ways to modify the cell wall surface of their host bacteria because of their high affinity to the cell walls and the huge number of binding sites (about 1E+07 per cell) on the walls. In view of the important roles of cell surface played in the process of biofilm formation, we will develop novel methods against S. aureus biofilm formation and elucidate the mechanisms behind by modifying S. aureus cell wall with different charged proteins and quorum sensing inhibiting molecular via CBDs of bacteriophage lysins. This research will generate new clues and targets for developing novel agents against S. aureus biofilm formation.