抗菌肽的活性机制及其分子设计研究进展

中国畜牧兽医

抗菌肽的活性机制及其分子设计研究进展

张庆华，王青，尚田田，赵志雨，徐彦召，胡建和

（河南科技学院动物科学学院，河南新乡 453003）

收稿日期:2013-12-23 出版日期:2014-05-20 发布日期:2014-06-25
通讯作者: 徐彦召（1984—），男，河南人，博士，从事动物微生物学、分子病毒学研究。胡建和（1968—），男，河南人，博士，从事动物微生物学、分子病毒学研究。 E-mail：haoxyz@163.com；Tel：0373-3040718
作者简介:张庆华（1988—），男，河南人，硕士生，研究方向：动物微生物学。
基金资助:
国家自然科学基金（31372469）。

Advances on the Studies of Antimicrobial Peptide’s Active Mechanism and its Molecular Design

ZHANG Qing-hua, WANG Qing, SHANG Tian-tian, ZHAO Zhi-yu, XU Yan-zhao, HU Jian-he

(College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China)

Received:2013-12-23 Online:2014-05-20 Published:2014-06-25

摘要/Abstract

摘要： 抗菌肽是生物体在抵抗外来微生物入侵时产生的一类防御性小肽，在自然界分布广泛，是机体先天免疫系统的重要组成部分。与传统的抗生素相比，抗菌肽分子质量小、水溶性好、热稳定性好、抗菌机理独特、具有广谱的抗细菌、抗病毒、抗真菌、抗肿瘤等活性，且不易诱发细菌产生耐药性等特点。随着细菌耐药问题不断出现及新型抗菌肽的陆续发现，抗菌肽的抗菌活性、溶血性及细胞毒性的机制已成为研究的热点。笔者主要对抗菌肽的分子改造及活性机制的最近研究进展进行阐述，以期为抗菌肽的分子设计改造和应用提供科学的参考依据。

关键词:

抗菌肽; 活性机制; 分子设计

Abstract: The antimicrobial peptides (AMPs) are a class of defense peptides that widely exist in nature, which are important components of the innate immune system. Compared to antibiotics, AMPs have some good quality, such as small molecular weight, good water-solubility, thermal stability and unique antibiotic mechanism. They can also restrain virus, fungus and even tumour. With the appearance of multidrug-resistant (MDR) bacteria and the increasing of new AMPs, the study focuses on it’s mechanism of biological activity. This paper summarizes the biological activity mechanism and molecular modification of AMPs, so as to provide theory basis for the molecular modification and the application of AMPs.

Key words: antimicrobial peptides; mechanism of activity; molecular design

张庆华，王青，尚田田，赵志雨，徐彦召，胡建和. 抗菌肽的活性机制及其分子设计研究进展[J]. 中国畜牧兽医.

ZHANG Qing-hua, WANG Qing, SHANG Tian-tian, ZHAO Zhi-yu, XU Yan-zhao, HU Jian-he. Advances on the Studies of Antimicrobial Peptide’s Active Mechanism and its Molecular Design[J]. .

参考文献

1 王兴顺，耿艺介，李文楚. 抗菌肽抗菌机制及其应用研究进展［J］. 微生物学免疫学进展，2012，40(4)：70～76.
2 刘显军，丁雪，陈静，等. 抗菌肽和抗生素对断奶仔猪生长性能的影响［J］. 中国畜牧兽医，2012，39(7)：252～256.
3 张志勇，尹大川，卢慧甍. 粗粒化模拟及其在生物膜研究领域的应用［J］. 生命化学，2010，3(5)：438～443.
4 赵建乐，李引乾. 牛抗菌肽及其基因工程的研究进展［J］. 中国兽医科学，2010，40(8)：873～879.
5 彭慧珍，罗振福，贺建华. 抗菌肽及其在畜牧业中的应用［J］. 饲料与畜牧，2008，4(5)：5055.
6 舒黛廉，任敏，王珏. 抗菌肽研究现状及其在畜牧业中的应用前景［J］. 中国畜牧兽医，2007，34(6)：100～104.
7 Avitabile C, Netti F, Orefice G, et al. Design, structural and functional characterization of a Temporin-1b analogue active against Gram negative bacteria［J］. Biochimica et Biophysica Acta (BBA)-General Subjects, 2013, 18(30): 3767～3775.
8 Brown K L, Poon G F, Birkenhead D, et al. Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses［J］. The Journal of Immunology, 2011, 186(9): 5497～5505.
9 Ehrenstein G, Lecar H. Electrically gated ionic channels in lipid bilayers［J］. QRev Biophys, 1977, 10(1): 1～34.
10 Fischbach M A, Walsh C T. Antibiotics for emerging pathogens［J］. Science, 2009, 325(5944): 1089～1093.
11 He Y, Lazaridis T. Activity determinants of helical antimicrobial peptides: A large-scale computational study［J］. PLoS One, 2013, 8(6): e66440.
12 Hood J L, Jallouk A P, Campbell N, et al. Cytolytic nanoparticles attenuate HIV-1 infectivity［J］. Antiviral Therapy, 2013, 18(5): 95～103.
13 Hultmark D, Engstrm A, Bennich H, et al. Insect immunity: Isolation and structure of cecropin D and four minor antibacterial components from Cecropia pupae［J］. European Journal of Biochemistry, 1982, 127(1): 207～217.
14 Lee K, Shin S, Kim K, et al. Antibiotic activity and structural analysis of the scorpion-derived antimicrobial peptide IsCT and its analogs［J］. Biochemical and Biophysical Research Communications, 2004, 323(2): 712～719.
15 Li M, Lai Y P, Villaruz A, et al. Gram-positive three-component antimicrobial peptide-sensing system［J］. Proceedings of the National Academy of Sciences, 2007, 104(22): 9469～9474.
16 Li S A, Lee W H, Zhang Y. Efficacy of OH-CATH30 and its analogs against drug-resistant bacteria in vitro and in mouse models［J］. Antimicrob Agents Chemother, 2012, 56(6): 3309～3317.
17 Li L R, Shi Y H, Cheserek M, et al. Antibacterial activity and dual mechanisms of peptide analog derived from cell-penetrating peptide against Salmonella typhimurium and Streptococcus pyogenes［J］. Applied Microbiology and Biotechnology, 2013, 97(4): 1711～1723.
18 López-Oyama A, Taboada P, Burboa M G, et al. Interaction of the cationic peptide bactenecin with mixed phospholipid monolayers at the air-water interface［J］. Journal of Colloid and Interface Science, 2011, 359(1): 279～288.
19 O’driscoll N, Labovitiadi O, Cushnie T, et al. Production and evaluation of an antimicrobial peptide-containing wafer formulation for topical application［J］. Current Microbiology, 2013, 66(3): 271～278.
20 Poirel L, Hombrouck A C, Freneaux C, et al. Global spread of New Delhi metallo-β-lactamase 1［J］. The Lancet Infectious Diseases, 2010, 10(12): 832.
21 Pouny Y, Rapaport D, Mor A, et al. Interaction of antimicrobial dermaseptin and its fluorescently labeled analogs with phospholipid membranes［J］. Biochemistry, 1992, 31(49): 12416～12423.
22 Powers J, Hancock Robert E W. The relationship between peptide structure and antibacterial activity［J］. Peptides, 2003, 24(11): 1681～1691.
23 Sarig H, Livne L, Held K V, et al. A miniature mimic of host defense peptides with systemic antibacterial efficacy［J］. The FASEB Journal, 2010, 24(6): 1904～1913.
24 Walther T H, Gottselig C, Grage S L, et al. Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism［J］. Cell, 2013, 152(1): 316～326.
25 Yang S T, Shin S Y, Lee C W, et al. Selective cytotoxicity following Arg-to-Lys substitution in tritrpticin adopting a unique amphipathic turn structure［J］. FEBS Letters, 2003, 540(1): 229～233.
26 Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: Isolation, characterization of two active forms, and partial cDNA sequence of a precursor［J］. Proceedings of the National Academy of Sciences, 1987, 84(15): 5449～5453.
27 Zhu W L, Lan H L, Park J, et al. Design and mechanism of action of a novel bacteria-selective antimicrobial peptide from the cell-penetrating peptide Pep-1［J］. Biochemical and Biophysical Research Communications, 2006, 349(2): 769～774.