壁虎cathelicidin抗菌肽的改造及其对金黄色葡萄球菌的作用研究

全球抗生素耐药愈发严重, 耐甲氧西林金黄色葡萄球菌(MRSA) 在全球大部分地区检出率已超过30%，耐万古霉素金黄色葡萄球菌也已大范围出现，亟待开发针对金黄色葡萄球菌的新型抗菌药物。抗菌肽具有强大且广谱的抗菌活性，可用于新型抗菌候选药物分子的研发。我们在抗菌肽发掘与设计改造方面经验丰富，1个抗菌肽已获批1.1类新药临床批文（CXHL1700235），针对多种微生物设计改造了抗菌肽，代表性成果发表在PNAS（2019）杂志。近期，我们从壁虎中鉴定了2个cathelicidin家族抗菌肽（GJ-CATH-1、2），初步研究它们在体外和体内可显著杀灭金黄色葡萄球菌。本项目拟在前期基础上进行抗菌肽GJ-CATH-1、2的设计改造，以期望提升对金黄色葡萄球菌的抗菌活性和特异性，缩短长度，减小毒性并提高稳定性。本研究为耐药金黄色葡萄球菌的治疗提供候选多肽药物分子，也为设计高效低毒的抗菌肽提供参考策略。

The emergence of antibiotic resistance poses the greatest health threats. Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in most parts of the world is more than 30%, and vancomycin-resistant S. aureus (VRSA) have also been emerged, crucial antimicrobials against S. aureus are desperately needed. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics due to their potent and broad-spectrum antimicrobial activities. We are well experienced in identification and design of AMPs, an excellent AMP named cathelicidin-BF has been authorized to start clinical trials in 2018 (approval number: CXHL1700235), and a designed peptide showed excellent activity against multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, the study has been published in the journal PNAS (2019). Recently, two cathelicidin-related peptides (GJ-CATH-1 and GJ-CATH-2) have been identified from Gekko japonicas, and they exhibited excellent activity against S. aureus in vitro and in vivo. Based on GJ-CATH-1 and GJ-CATH-2, the present project will design new AMPs with enhanced antimicrobial activity and specificity against S. aureus, abbreviated peptide sequence, decreased toxic side effects and increased stability. The project will provide promising drug candidates in the battle against MDR S. aureus and valuable information for the design of peptide drug.