Grafskaia Ekaterina N, Polina Nadezhda F, Babenko Vladislav V, Kharlampieva Daria D, Bobrovsky Pavel A, Manuvera Valentin A, Farafonova Tatyana E, Anikanov Nikolay A, Lazarev Vassili N
* Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutskii per. 9, Dolgoprudny, Moscow 141700, Russia.
† Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 1a, Malaya Pirogovskaya Street, Moscow 119435, Russia.
J Bioinform Comput Biol. 2018 Apr;16(2):1840006. doi: 10.1142/S0219720018400061. Epub 2018 Jan 3.
As essential conservative component of the innate immune systems of living organisms, antimicrobial peptides (AMPs) could complement pharmaceuticals that increasingly fail to combat various pathogens exhibiting increased resistance to microbial antibiotics. Among the properties of AMPs that suggest their potential as therapeutic agents, diverse peptides in the venoms of various predators demonstrate antimicrobial activity and kill a wide range of microorganisms. To identify potent AMPs, the study reported here involved a transcriptomic profiling of the tentacle secretion of the sea anemone Cnidopus japonicus. An in silico search algorithm designed to discover toxin-like proteins containing AMPs was developed based on the evaluation of the properties and structural peculiarities of amino acid sequences. The algorithm revealed new proteins of the anemone containing antimicrobial candidate sequences, and 10 AMPs verified using high-throughput proteomics were synthesized. The antimicrobial activity of the candidate molecules was experimentally estimated against Gram-positive and -negative bacteria. Ultimately, three peptides exhibited antimicrobial activity against bacterial strains, which suggests that the method can be applied to reveal new AMPs in the venoms of other predators as well.
作为生物体内固有免疫系统的重要保守组成部分,抗菌肽(AMPs)可以补充那些越来越难以对抗各种对微生物抗生素耐药性增强的病原体的药物。在表明其作为治疗剂潜力的抗菌肽特性中,各种捕食者毒液中的多种肽表现出抗菌活性,并能杀死多种微生物。为了鉴定有效的抗菌肽,本文报道的研究对海葵日本刺冠海葵触手分泌物进行了转录组分析。基于对氨基酸序列特性和结构特点的评估,开发了一种旨在发现含有抗菌肽的毒素样蛋白的计算机搜索算法。该算法揭示了海葵中含有抗菌候选序列的新蛋白质,并合成了10种经高通量蛋白质组学验证的抗菌肽。通过实验评估了候选分子对革兰氏阳性和阴性细菌的抗菌活性。最终,三种肽对细菌菌株表现出抗菌活性,这表明该方法也可用于揭示其他捕食者毒液中的新型抗菌肽。