绿色气球菌噬菌体新型裂解酶AVPL的生物学特性及其跨菌种抗葡萄球菌的分子机制

病原细菌的超强、广谱耐药性已成为严重威胁医学、兽医学、公共卫生和健康养殖的重要问题，研发新型抗菌药物刻不容缓。噬菌体裂解酶对细菌具有高效和特异的杀菌活性，是新概念的抗菌物质，但其特异性导致的杀菌谱单一是影响应用的关键制约因素。本课题组前期分离到国内外首个绿色气球菌的噬菌体，其裂解酶AVPL与数据库中所有蛋白的同源性均不足20%，更有趣的是，AVPL对绿色气球菌以外的多种葡萄球菌（包括金黄色葡萄球菌和表皮葡萄球菌等）也表现出广谱、高效的抗菌活性。那么，AVPL具有哪些独特的生物学性质，其发挥跨菌种抗菌活性的分子机制是如何实现的？为了回答该科学问题，本项目将深入研究AVPL的生物学特性，重点利用晶体衍射和分子对接等解析其三维结构、揭示其发挥广谱抗菌活性的分子机制。该项目将为针对葡萄球菌和绿色气球菌新型抗菌药物的研发建立基础平台，也为革兰氏阳性菌广谱裂解酶的分子设计奠定坚实的理论与实验基础。

The strong and broad-spectrum antibiotic-resistance of pathogenic bacteria is a serious problem that threatens the human medicine, veterinary medicine, public health and healthy farming. Thus, it is an urgent need to develop new antibacterial drugs. Phage-derived lysin is a type of antibacterial agent which can efficiently and specificly kill bacteria. However, the narrow bactericidal spectrum of lysin due to the specificity is a major constraint on affecting its therapeutic application. In our previous studies, the first phage (AVP) infecting Aerococcus viridans was isolated. AVPL, the lysin of AVP, shows less than 20% identity to all proteins in the database. What is more interesting is, besides A. viridans, AVPL also displays strong and broad-spectrum bactericidal activity against staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis etc. Comparing with other phage lysins, what features does AVPL possess? How AVPL plays the cross-species bactericidal activity? To answer this question, we will further study the biological characteristics of AVPL, analyze the three-dimensional structure of AVPL, and finally reveal the molecular mechanism of its strong and broad-spectrum bactericidal activity, by crystal diffraction and molecular docking etc. The research will not only establish a basic platform for the development of new antibacterial drugs against staphylococci and A. viridans, but also provide substantial theoretical and experimental bases for the design of lysin which displays strong and broad-spectrum bactericidal activity against Gram-positive bacteria.