Mylonakis Eleftherios, Podsiadlowski Lars, Muhammed Maged, Vilcinskas Andreas
Division of Infectious Disease, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA.
Institute of Evolutionary Biology and Zooecology, University of Bonn, Bonn, Germany.
Philos Trans R Soc Lond B Biol Sci. 2016 May 26;371(1695). doi: 10.1098/rstb.2015.0290.
Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides.The article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.
抗菌肽(AMPs)是具有抗菌活性的短蛋白。已知的大部分抗菌肽源自昆虫,不同物种中这些分子的数量和多样性差异很大。昆虫抗菌肽是解决当前抗生素局限性的潜在替代抗生素来源,当前抗生素的局限性是由多重耐药病原体的出现和传播导致的。为了更深入地了解抗菌肽,我们通过绘制其系统发育分布来研究昆虫抗菌肽的多样性和进化,这使我们能够预测选定抗菌肽家族的进化起源,并识别进化上保守的家族和特定分类群的家族。此外,我们强调了使用线虫秀丽隐杆线虫作为全动物模型,采用高通量筛选方法来鉴定对包括鲍曼不动杆菌和耐甲氧西林金黄色葡萄球菌在内的人类病原体有效的抗菌肽。我们还讨论了抗菌肽的潜在医学应用,包括它们作为传统抗生素在异位治疗中的替代品的用途、它们与抗生素联合使用以恢复多重耐药病原体的敏感性,以及它们作为克服治疗性肽缺点的拟肽药物合理设计模板的用途。本文是主题为“节肢动物抗菌肽的进化生态学”特刊的一部分。