近日中国科学院昆明动物研究所抗菌肽与天然免疫研究实验室赖仞研究小组在抗菌肽的研究方面又取得新进展，他们在金环蛇的体内发现一种蛇Cathelicidin具有抗菌的潜在功效。该成果公布在PloS  ONE上。

据悉，Cathelicidin是在哺乳动物体内发现的一类结构多变的抗微生物肽,因在表达的信号肽与成熟肽之间含有一高度保守的cathelin肽段而自成一家族。Cathelicidin和防御素一样，也是宿主免疫防御系统的重要组成部分。除了主要的抗菌活性以外，Cathelicidin还具有抑制组织损伤,促进创伤修复,结合内毒素，诱导血管生成等多种生物学功能。

近期来，在非哺乳动物的体内也发现有Cathelicidin的存在，已经在鸡和鱼的体内发现。但是一直没有在除哺乳动物外的其他脊椎动物中报道发现。

赖仞小组在金环蛇体内发现Cathelicidin，命名为Cathelicidin-BF，并构建了Cathelicidin-BF的cDNA文库。这些证实爬行动物体内也存在Cathelicidin。赖仞教授带领的研究小组对Cathelicidin-BF的结构和功能进行了深入的研究。

研究发现，Cathelicidin-BF在结构与功能上与典型的Cathelicidin具有差别，这为研究Cathelicidins的进化历程提供了实物依据。Cathelicidin-BF还具有抗微生物活性，研究者认为它可能成为优秀的临床抗生素药物，或是农药。

推荐原始出处：

PLoS ONE 3(9): e3217. doi:10.1371/journal.pone.0003217

Snake Cathelicidin from Bungarus fasciatus Is a Potent Peptide Antibiotics

Yipeng Wang1,4#, Jing Hong2,4#, Xiuhong Liu3#, Hailong Yang1,4, Rui Liu3, Jing Wu1,4, Aili Wang3, Donghai Lin2*, Ren Lai1,3*

1 Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China, 2 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 3 Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Life Sciences College of Nanjing Agricultural University, Nanjing, Jiangsu, China, 4 Graduate School of the Chinese Academy of Sciences, Beijing, China

Abstract

Background

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules of innate immunity, which are firstly found in mammalians. Recently, several cathelicidins have also been found from chickens and fishes. No cathelicidins from other non-mammalian vertebrates have been reported.

Principal Findings

In this work, a cathelicidin-like antimicrobial peptide named cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and its cDNA sequence was cloned from the cDNA library, which confirm the presence of cathelicidin in reptiles. As other cathelicidins, the precursor of cathelicidin-BF has cathelin-like domain at the N terminus and carry the mature cathelicidin-BF at the C terminus, but it has an atypical acidic fragment insertion between the cathelin-like domain and the C-terminus. The acidic fragment is similar to acidic domains of amphibian antimicrobial precursors. Phylogenetic analysis revealed that the snake cathelicidin had the nearest evolution relationship with platypus cathelicidin. The secondary structure of cathelicidin-BF investigated by CD and NMR spectroscopy in the presence of the helicogenic solvent TFE is an amphipathic α-helical conformation as many other cathelicidins. The antimicrobial activities of cathelicidin BF against forty strains of microorganisms were tested. Cathelicidin-BF efficiently killed bacteria and some fungal species including clinically isolated drug-resistance microorganisms. It was especially active against Gram-negative bacteria. Furthermore, it could exert antimicrobial activity against some saprophytic fungus. No hemolytic and cytotoxic activity was observed at the dose of up to 400 μg/ml. Cathelicidin-BF could exist stably in the mice plasma for at least 2.5 hours.

Conclusion

Discovery of snake cathelicidin with atypical structural and functional characterization offers new insights on the evolution of cathelicidins. Potent, broad spectrum, salt-independent antimicrobial activities make cathelicidin-BF an excellent candidate for clinical or agricultural antibiotics.