近日中國科學(xué)院昆明動物研究所抗菌肽與天然免疫研究實(shí)驗(yàn)室賴仞研究小組在抗菌肽的研究方面又取得新進(jìn)展,，他們在金環(huán)蛇的體內(nèi)發(fā)現(xiàn)一種蛇Cathelicidin具有抗菌的潛在功效,。該成果公布在PloS ONE上。
據(jù)悉,，Cathelicidin是在哺乳動物體內(nèi)發(fā)現(xiàn)的一類結(jié)構(gòu)多變的抗微生物肽,因在表達(dá)的信號肽與成熟肽之間含有一高度保守的cathelin肽段而自成一家族,。Cathelicidin和防御素一樣，也是宿主免疫防御系統(tǒng)的重要組成部分,。除了主要的抗菌活性以外,，Cathelicidin還具有抑制組織損傷,促進(jìn)創(chuàng)傷修復(fù),結(jié)合內(nèi)毒素，誘導(dǎo)血管生成等多種生物學(xué)功能,。
近期來,，在非哺乳動物的體內(nèi)也發(fā)現(xiàn)有Cathelicidin的存在，已經(jīng)在雞和魚的體內(nèi)發(fā)現(xiàn),。但是一直沒有在除哺乳動物外的其他脊椎動物中報(bào)道發(fā)現(xiàn),。
賴仞小組在金環(huán)蛇體內(nèi)發(fā)現(xiàn)Cathelicidin，命名為Cathelicidin-BF,，并構(gòu)建了Cathelicidin-BF的cDNA文庫,。這些證實(shí)爬行動物體內(nèi)也存在Cathelicidin。賴仞教授帶領(lǐng)的研究小組對Cathelicidin-BF的結(jié)構(gòu)和功能進(jìn)行了深入的研究,。
研究發(fā)現(xiàn),，Cathelicidin-BF在結(jié)構(gòu)與功能上與典型的Cathelicidin具有差別，這為研究Cathelicidins的進(jìn)化歷程提供了實(shí)物依據(jù),。Cathelicidin-BF還具有抗微生物活性,，研究者認(rèn)為它可能成為優(yōu)秀的臨床抗生素藥物，或是農(nóng)藥,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
