Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada.
Crit Rev Biotechnol. 2012 Jun;32(2):143-71. doi: 10.3109/07388551.2011.594423. Epub 2011 Nov 11.
Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.
危及生命的传染病正逐渐在全球范围内引发危机,由于抗生素耐药菌株的出现,有效治疗这些疾病变得越来越困难。抗菌肽 (AMPs) 是一种古老的先天免疫形式,普遍存在于所有生物体中,是抵御入侵病原体的主要第一道防线。AMPs 的独特多样的功能和结构引起了科学家们的极大关注,既有助于理解先天免疫系统的基本生物学,也有助于设计新型抗感染药物的分子模板。AMPs 是基因编码的短肽(<100 个氨基酸),具有疏水性和阳离子性氨基酸的空间排列,表现出广谱的抗菌活性。AMPs 和微生物已经经历了数亿年的自然进化。尽管有这种长期的共同进化史,但 AMPs 并没有完全失去杀死或抑制微生物的能力,微生物也没有学会避免 AMPs 的致命打击。因此,AMPs 有可能提供一个重要的突破,并为一类新的抗生素奠定基础。在这篇综述中,我们将概述阳离子抗菌肽的起源、结构、功能和作用机制,这些肽在人类中高度表达和发现,以及哺乳动物中广泛存在且特征明显的 AMPs 的简要讨论,此外还将讨论 AMPs 的药物方面和其他功能。