多黏菌素耐药性流行背景下抗菌肽药物研究进展

Research progress in the development of antimicrobial peptides in the epidemic of polymyxin resistance

摘要:

抗菌肽(antimicrobial peptides, AMPs)因高效广谱性、低免疫原性、稳定持久性以及靶点多样性，在临床治疗、畜牧养殖、食品加工保藏领域应用前景良好。近年来，医源、养殖环境中脂肽类抗生素多黏菌素耐药性流行性被陆续揭示并引发关注，这些重要发现使得抗菌肽在产业应用、临床使用和研究发展方面产生了重大变革。本文综述了代表性AMPs的性质、分类及合成组装机制，归纳了AMPs杀菌模式多样性和耐药性形成的遗传本质及调控因素，系统性地比较了纯培养检测和高通量识别AMPs药敏性及耐药基因的技术方法，展望了复敏增效联合佐剂挖掘鉴定、机器学习模式识别指导下生物合成和化学修饰实现分子改造、药效强化以预防和控制耐药性产生与流行的学科前沿。深入认识抗菌肽的构效关系及多样化耐药机制有助于开发杀菌效果好、毒副作用小的新型抗菌肽以应对多重耐药细菌挑战，为食品安全、公共健康建设提供参考。

Abstract:

Antimicrobial peptides (AMPs), with broad antimicrobial spectra, high efficacy, low immunogenicity, high sustainability, and diverse killing targets, demonstrate promising application prospects in clinical medicine, animal farming, and food processing and storage. Polymyxin (a lipopeptide AMP) resistance and its spread have been found in nosocomial and environmental micro-niches, resulting in significant changes in industrial/breeding application, clinical therapy, and development of AMPs. This review summarized the recent research advances in AMPs regarding the general properties, classification, synthesis/assembly, and genetic basis and regulatory factors of the diverse antibacterial patterns and antibiotic resistance. Furthermore, we systematically compared the antimicrobial susceptibility assessment and antibiotic resistance gene identification between pure culture and high-throughput sequencing and made an outlook on the enhancement approaches to prevent and control antibiotic resistance by focusing on re-sensitization adjuvants, chemical modification, and metabolic engineering driven by machine learning. Delving into the structure-function relationships and resistance mechanisms of AMPs would benefit the development of drugs with higher efficiency and lower side effects, facilitating food safety and public health.