Haney Evan F, Hancock Robert E W
Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, British Columbia, Canada V6T 1Z4.
Biopolymers. 2013 Nov;100(6):572-83. doi: 10.1002/bip.22250.
The increasing threat of antibiotic resistance in pathogenic bacteria and the dwindling supply of antibiotics available to combat these infections poses a significant threat to human health throughout the world. Antimicrobial peptides (AMPs) have long been touted as the next generation of antibiotics capable of filling the anti-infective void. Unfortunately, peptide-based antibiotics have yet to realize their potential as novel pharmaceuticals, in spite of the immense number of known AMP sequences and our improved understanding of their antibacterial mechanism of action. Recently, the immunomodulatory properties of certain AMPs have become appreciated. The ability of small synthetic peptides to protect against infection in vivo has demonstrated that modulation of the innate immune response is an effective strategy to further develop peptides as novel anti-infectives. This review focuses on the screening methods that have been used to assess novel peptide sequences for their antibacterial and immunomodulatory properties. It will also examine how we have progressed in our ability to identify and optimize peptides with desired biological characteristics and enhanced therapeutic potential. In addition, the current challenges to the development of peptides as anti-infectives are examined and the strategies being used to overcome these issues are discussed.
致病细菌中抗生素耐药性的威胁日益增加，而用于对抗这些感染的抗生素供应却日益减少，这对全球人类健康构成了重大威胁。抗菌肽（AMPs）长期以来一直被誉为能够填补抗感染空白的下一代抗生素。不幸的是，尽管已知的抗菌肽序列数量众多，且我们对其抗菌作用机制有了更深入的了解，但基于肽的抗生素尚未发挥出其作为新型药物的潜力。最近，某些抗菌肽的免疫调节特性已受到关注。小型合成肽在体内预防感染的能力表明，调节固有免疫反应是进一步将肽开发为新型抗感染药物的有效策略。本综述重点关注用于评估新型肽序列抗菌和免疫调节特性的筛选方法。它还将探讨我们在识别和优化具有所需生物学特性及增强治疗潜力的肽方面取得了哪些进展。此外，还将研究肽作为抗感染药物开发目前面临的挑战，并讨论用于克服这些问题的策略。
