近日，中国科学院昆明动物研究所在动物来源的抗菌肽研究方面取得重要进展，在单个两栖动物个体中发现了107种新型的抗菌肽类似多肽，占全世界已知抗菌肽总数的10％左右，是目前世界上发现的最丰富的抗菌肽资源。该研究成果日前在《分子细胞蛋白质组学》上发表。
抗菌肽是一类很难导致微生物耐药性的新型抗感染药物多肽，目前世界上已知的抗菌肽共有1200多种。中国科学院昆明动物研究所研究员赖仞领导的研究团队在单个两栖动物个体中发现了107种新型的抗菌肽类似多肽，占全世界已知抗菌肽总数的10％左右，并克隆了372条抗菌肽基因，分属于30个不同的多肽家族，是目前世界上发现的最丰富抗菌肽资源。他们还对不同家族的抗菌肽样多肽进行了抗菌机制研究。有关人士介绍，该成果为开发设计新型抗感染药物提供了丰富的多肽来源，对推动新型抗感染药物研发具有一定意义。
部分英文原文：
Anti-infection peptidomics of amphibian skin
Jianxu Lia, h, ¶, Xueqing Xu a, h, ¶, Chunhua Xu b, Weiping Zhou c, h, Keyun Zhang b, Haining Yu f, Yaping Zhangc, Yongtang Zheng d, Huw H Reese, Ren Laia, b, * Dongming Yang g, Jing Wu a, h
aBiotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; bKey Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Life Sciences College of Nanjing Agricultural University, Nanjing 210095, Jiangsu, China; cKey Laboratory of Cellular and Molecular Evolution of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; dLaboratory of Molecular Immunopharmacology Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; eSchool of Biological Sciences University of Liverpool, Liverpool L69 7ZB, United Kingdom; f College of Life Sciences of Heibei Normal University, Shijiazhuang 050016, Hebei, China; gBeijing Institute of Biomedicine, 15 Xinjiangongmen rd., Beijing 100091, China; hGraduate School of the Chinese Academy of Sciences, Beijing100009, China.
Running head: antimicrobial bio-weapon array of peptides
¶ These authors have the same contribution to this paper
* Author to whom correspondence should be addressed:
Dr Ren Lai
Kunming Institute of Zoology, Chinese Academy of Sciences,
Kunming 650223, Yunnan, China
Tel : +86-871-5196202; fax: +86-871-5191823
E-mail: rlai@mail.kiz.ac.cn
Summary
Peptidomics and genomics analyses were used to study an anti-infection array of peptides of amphibian skin. 372 cDNA sequences of antimicrobial peptides have been characterized from a single individual skin of the frog, Odorrana grahami, encoding 107 novel antimicrobial peptides. This contribution almost triples the number of currently reported amphibian antimicrobial peptides. The peptides can be organized into 30 divergent groups, including 24 novel groups. The diversity in peptide coding cDNA sequences is, to our knowledge, the most extreme yet described for any animal. The patterns of diversification, suggest that point mutations, as well as insertion, deletion, and “shuffling” of oligonucleotide sequences have been responsible. The diversity of antimicrobial peptides may have resulted from the diversity of microorganisms. These diverse peptides exhibit both diverse secondary structure and “host-defense” properties. Such extreme antimicrobial peptide diversity in a single amphibian species is amazing. This makes us have to reconsider the strong capability of innate immunity and molecular genetics of amphibian ecological diversification and doubt the general opinion that 20-30 different antimicrobial peptides can protect an animal because of the relatively wide specificity of the peptide antibiotics. Their antimicrobial mechanisms were investigated. They exert their antimicrobial functions by various means, including forming lamellar mesosome-like structures, peeling off the cell walls, forming pores, and inducing DNA condensation. With respect to the development of antibiotics, these peptides provide potential new templates to further explore.
Key Words: antimicrobial peptides; innate immunity; diversity; amphibian; peptidomics
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