Department of Biopathology and Clinical Microbiology, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Lancet Infect Dis. 2020 Sep;20(9):e216-e230. doi: 10.1016/S1473-3099(20)30327-3. Epub 2020 Jul 9.
Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune response. Broad bacterial susceptibility to antimicrobial peptides offers an additional tool to expand knowledge about the evolution of antimicrobial resistance. Structural and functional limitations, combined with a stricter regulatory environment, have hampered the clinical translation of antimicrobial peptides as potential therapeutic agents. Existing computational and experimental tools attempt to ease the preclinical and clinical development of antimicrobial peptides as novel therapeutics. This Review identifies the benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens, highlights advances in the deployment of novel promising antimicrobial peptides, and underlines the needs and priorities in designing focused development strategies taking into account the most advanced tools available.
抗菌药物耐药性的快速增长和全球蔓延,使得人们更加迫切地需要开发新型抗菌药物。与传统抗生素相比,抗菌肽具有明显优势,包括耐药性产生较慢、广谱抗生物膜活性以及能够有利地调节宿主免疫反应。抗菌肽对广泛的细菌具有敏感性,这为进一步了解抗菌药物耐药性的进化提供了额外的手段。结构和功能的局限性,再加上更严格的监管环境,阻碍了抗菌肽作为潜在治疗药物向临床的转化。现有的计算和实验工具试图缓解抗菌肽作为新型治疗药物的临床前和临床开发。本综述确定了使用抗菌肽对抗多药耐药病原体的益处、挑战和机遇,强调了新型有前途的抗菌肽的应用进展,并强调了在设计集中开发策略时,需要考虑到现有最先进的工具,确定需求和优先事项。