耐甲氧西林金黄色葡萄球菌（MRSA）在全球范围内的快速蔓延和致病性的不断增强，严重威胁着人类的健康，迫切需要更有效的抗生素来治疗MRSA感染。申请人从60株海绵共附生微生物中筛选出3种抗MRSA活性最强的木霉属Trichoderma真菌，对其活性馏分的LC-QTOF-MS分析发现这些馏分富含肽类，并从一株真菌SM16中分离鉴定了5个分子量大于1100的新链肽，其中抗MRSA活性最强的链肽MIC50值小于0.5μg/mL。.本项目拟在此基础上，采用UPLC-QTOF-MS和抗MRSA活性筛选相结合的方法，从其他海绵共附生Trichoderma真菌中高效发现的抗MRSA活性更强的肽类，采用QTOF-MS/MS、NMR和Mafey化学衍生等方法确定其氨基酸序列和绝对构型，阐明其构效关系，确定活性序列片段，发现1-2个高效低毒的的抗MRSA活性多肽，为新型海洋抗MRSA药物的研发奠定基础。

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has been increasing fast and spreading in the whole world rapidly. At the same time, the pathogenicity of MRSA is also becoming so strong that the number of antibiotics effective against MRSA infections is decreasing very fast. MRSA infections is globally becoming more dangerous to human beings than ever before. Therefore, it is very urgent to discover new and more effective antibiotics to treat MRSA infections. In our search for new anti-MRSA compounds from marine sponge-associated microorganisms, the applicant has isolated 60 strains of microbes from four marine sponges collected from the South China Sea sponges. Anti-bacterial activity evaluation of the 60 crude extracts showed that the extracts of three strains of fungi belonging to the genus of Trichoderma showed potent anti-MRSA activity. Further UPLC-QTOF-MS/MS analysis of their subfractions revealed that these fractions contained peptides. So far, five new linear peptides with molecular weights more than 1100 Da have been isolated from Trichoderma sp. SM16 and structurally determined. All the five peptides showed potent anti-MRSA activity with MIC values <0.5 μg/mL..Based on the above results, the applicant is going to efficiently discover new anti-MRSA peptides from other sponge-associated Trichoderma fungi by combination of UPLC-QTOF-MS/MS analysis and anti-MRSA screening assays. The sequences of amino acids of the isolated active peptides will be determined by QTOF-MS/MS coupled with NMR analysis, while the absolute configurations of amino acids will be assigned by chemical reactions with Marfey’s reagents. The structure activity relationship of active peptides will be investigated in order to disclose the functional sequence fragments. One or two anti-MRSA leading peptides, which are more effective against MRSA and less toxic to human beings, will be discovered. These findings will lay foundation for developing new anti-MRSA peptide drugs.