噬菌体裂解酶可以特异、高效的裂解细菌，有着与抗生素完全不同的作用机制，是极具潜力的新概念抗菌物质。前期在国家自然基金重点课题的资助下获得了对耐药性金黄色葡萄球菌具有广谱、高效裂解活性的噬菌体裂解酶（LysGH15），并进一步揭示了LysGH15的三维结构与分子作用机制，其在体外和体内均表现出良好的治疗效果。但作为一种新型多肽药物，其进入体内后的抗原性、与组织细胞的相互作用及其体内代谢规律尚不清楚，而这是其作为药用必须回答的科学问题。因此，本项目将深入研究该裂解酶进入体内的抗原性及其对机体的影响；重点通过经典的同位素标记示踪法、免疫学鉴定法、色谱-质谱串联检测等方法，深入研究该裂解酶在体内吸收、分布、代谢和排泄等药代动力学特性，为将LysGH15作为治疗耐药金葡菌感染的新型抗菌多肽药物提供坚实的理论与实验基础。

Lysin is a kind of hydrolytic enzyme which is encoded by phage and able to lyse bacteria specifically and efficiently. The bactericidal mechanism of lysin is different from that of antibiotics. Bacteria that are resistant to antibiotics also exhibit sensitive to lysin. Hence, lysin belongs to a novel antibacterial agent. In the previous studies supported by the National Natural Science Foundation of China, we obtained a lysin named LysGH15 (encoded by phage GH15) which shows broad host-range and strong lytic activity against multi-drug resistant Staphylococcal aureus in vitro and in vivo. LysGH15 shows great potential as alternative treatment strategy for infections caused by multi-drug resistant S. aureus. The three-dimensional structure and molecular function mechanism of LysGH15 have been further revealed. All these researches laid solid foundation for the development of LysGH15 as a novel antibacterial. However, the antigenicity and the pharmacokinetic of LysGH15 have not been revealed. It was the scientific question that must be resolve for the application of LysGH15. Thus, in the following work, the antigenicity and the application formulation of LysGH15 will be studied. More importantly, the pharmacokinetic features of LysGH15, including the characterizations of adsorption, distribution, metabolism and excretion in vivo, will be revealed systematically by methods of isotope-labeling, ELISA, chromatography- and mass- spectrography. These studies will provide theoretical and experimental basis for utilization of LysGH15 as novel polypeptide drug in the treatment of infections caused by S. aureus, especially by drug resistant S. aureus.