Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2012, Vol. 32 Issue (05): 97-106    
综述     
病原微生物对抗菌肽抗性机制的研究进展
陈武1, 黎定军2,3, 丁彦3, 张旭4, 肖启明3, 周清明1
1. 湖南农业大学农学院 长沙 410128;
2. 湖南广播电视大学 长沙 410004;
3. 湖南农业大学生物安全科技学院 湖南 410128;
4. 上海交通大学药学院 上海 200240
Progress in the Resistance Mechanisms of Pathogenic Microorganism against Antimicrobial Peptide
CHEN Wu1, LI Ding-jun2,3, DING Yan3, ZHANG Xu4, XIAO Qi-ming3, ZHOU Qing-ming1
1. Postdoctoral Research Station of Crops Science, College of Agriculture, Hunan Agricultural University (HNAU, Changsha 410128, China;
2. Hunan Radio and Television University, Changsha 410004, China;
3. College of Bio-safty Science and Technology, HNAU, Changsha 410128, China;
4. School of Pharmacy, Shanghai Jiaotong University, Minhang, Shanghai 200240, China
 全文: PDF(494 KB)   HTML
摘要:

抗菌肽(antimicrobial peptides, AMPs)是生物先天免疫系统的重要组成部分,可帮助宿主有效应对病原细菌、真菌和病毒等微生物的胁迫,被认为是医疗、食品加工和农业领域最具前途和潜力的抗生素替代物。病原微生物在与抗菌肽的互作中进化出了多种有针对性的抗性机制,从病原微生物对AMPs的感应与基因调控、细胞壁/膜成分的修饰、分泌蛋白酶降解及利用外排泵排出4个方面综述了国内外的研究进展,并对AMPs类制品的研究前景进行了讨论与展望。

关键词: 抗菌肽病原微生物抗性机制感应与调控细胞壁/膜修饰胞外蛋白酶外排泵    
Abstract:

As part of the innate immunity system of host organism, antimicrobial peptides (AMPs) possess a wide spectrum of antimicrobial activity against eubacteria, fungi and eukaryotic parasites. AMPs are considered as one of potential alternates to the classical antibiotics in medicine, agriculture and food industry. The pathogenic microorganisms have correspondingly developed a defense system against the actions of AMPs during the co-evolution between the hosts and the pathogens. Recent discoveries on the resistance mechanism of pathogenic microorganism against AMPs, including sensing and gene regulation, modification of cell wall and/or plasma membrane, degradation of secreted proteases, as well as efflux pump by transporter proteins are discussed. Further, the perspectives of future research on AMP productions were proposed.

Key words: Antimicrobial peptide    Pathogenic microorganism    Resistance mechanism    Sensing and gene regulation    Modification of cell wall and membrane    Protease    Efflux pumps
收稿日期: 2012-01-13 出版日期: 2012-05-25
ZTFLH:  Q939.9  
基金资助:

国家"863"计划(2009AA10Z403)、国家自然科学基金项目(31101482)、长沙市科技攻关资金专项(K1109008-21)资助项目

通讯作者: 周清明     E-mail: zqm0618@yahoo.com.cn
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  

引用本文:

陈武, 黎定军, 丁彦, 张旭, 肖启明, 周清明. 病原微生物对抗菌肽抗性机制的研究进展[J]. 中国生物工程杂志, 2012, 32(05): 97-106.

CHEN Wu, LI Ding-jun, DING Yan, ZHANG Xu, XIAO Qi-ming, ZHOU Qing-ming. Progress in the Resistance Mechanisms of Pathogenic Microorganism against Antimicrobial Peptide. China Biotechnology, 2012, 32(05): 97-106.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2012/V32/I05/97


[1] Yeaman M R, Yount N Y. Mechanisms of antimicrobial peptide action and resistance. Pharmacolog Rev, 2003,55(1): 27-55.

[2] Mota-Meiral M, Morency H, Lavoie M C. In vivo activity of mutacin B-Ny266. J Antimicrob Chemother, 2005,56(5): 869-871.

[3] Nijnik A, Hancock R E W. Host defence peptides: antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections. Emerging Health Threats J, 2009,2: e1.

[4] 黎定军, 陈武, 罗宽. 侧孢芽孢杆菌抑菌物质性质. 湖南农业大学学报(自然科学版), 2007, 33(4): 471-474. Li D J, Chen W, Luo K. On characteristics of the antibiotics secreted by Bacillus laterosporus strain 2-Q-9. J Hunan Agricultural University (Natural Sciences), 2007, 33(4): 471-474.

[5] Keymanesh K, Soltani S, Sardari S. Application of antimicrobial peptides in agriculture and food industry. World J Microbiol Biotechnol, 2009, 25(6): 933-944.

[6] Montesinos E. Antimicrobial peptides and plant disease control. FEMS Microbiol Lett, 2007,270: 1-11.

[7] Zasloff M. Antimicrobial peptides of multicellular organisms. Nature, 2002,415(6870): 389-395.

[8] Toke O. Antimicrobial peptides: new candidates in the fight against bacterial infections. Biopolymers, 2005, 80(6):717-735.

[9] Venugopal D, Klapper D, Srouji A H, et al. Novel antimicrobial peptides that exhibit activity against select agents and other drug resistant bacteria. Bioorg Med Chem, 2010,18(14):5137-5147.

[10] Oyston P C F, Fox M A, Richards S J. Novel peptide therapeutics for treatment of infections. J Med Microbiol, 2009,58(Pt 8):977-987.

[11] Hong R W, Shchepetov M, Weiser J N, et al. Transcriptional profile of the Escherichia coli response to the antimicrobial insect peptide cecroin A. Antimicrob Agents Chemother, 2003, 47:1-6.

[12] Bell G, Gouyon P H. Arming the enemy: the evolution of resistance to self-proteins. Microbiol, 2003, 149(Pt 6):1367-1375.

[13] Perron G G, Zasloff M, Bell Graham. Experimental evolution of resistance to an antimicrobial peptide. Proc Biol Sci B, 2006, 273(1583):251-256.

[14] Bader M W, Sanowar S, Daley M E, et al. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell, 2005,122(3):461-472.

[15] Guina T, Yi E C, Wang H, et al. A PhoP-Regulated Outer Membrane Protease of Salmonella enterica Serovar Typhimurium Promotes Resistance to Alpha-Helical Antimicrobial Peptides. Bacteriol, 2000, 182(14):4077-4086.

[16] Gunn J S. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol, 2008,16(6):284-290.

[17] Li M, Cha D J, Lai Y P, et al. The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol Microbiol, 2007a, 66(5):1136-1147.

[18] Li M, Lai Y P, Villaruz A E, et al. Gram-positive three-component antimicrobial peptide-sensing system. Proc Natl Acad Sci U S A, 2007b, 104(22): 9469-9474.

[19] Kox L F, Wosten M M, Groisman E A. A small protein that mediates the activation of a two-component system by another two-component system. EMBO J, 2000,19(8): 1861-1872.

[20] Kato A, Groisman E A. Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor. Genes Dev, 2004, 18(18): 2302-2313.

[21] Pietiäinen M, Gardemeister M, Mecklin M, et al. Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems.Microbiol, 2005,151(5):1577-1592.

[22] Kovács M, Halfmann, Fedtke I, et al. A Functional dlt Operon, encoding proteins required for incorporation of D-alanine in teichoic acids in Gram-positive bacteria, confers resistance to cationic antimicrobial peptides in Streptococcus pneumoniae. J Bacteriol, 2006, 188(16): 5759-5805.

[23] Peschel A. How do bacteria resist human antimicrobial peptides? Trends Microbiol, 2002, 10(4): 179-186.

[24] Abachin E, Poyart C, Pellegrini E, et al. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol Microbiol, 2002, 43(1): 1-14.

[25] McBride S M, Sonenshein A L. The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile. Microbiology, 2011,157(Pt5):1457-1465.

[26] Abi Khattar Z, Rejasse A, Destoumieux-Garzón D, et al. The dlt operon of Bacillus cereus is required for resistance to cationic antimicrobial peptides and for virulence in insects. J Bacteriol, 2009, 191 (22) :7063-7073.

[27] Samant S, Hsu F F, Neyfakh A A, et al. The Bacillus anthracis protein MprF is required for synthesis of lysylphosphatidylalycerols and for resistance to cationic antimicrobial peptides. J Bacteriol, 2009, 191(4): 1311-1319.

[28] Ernst C M, Peschel A. Broad-spectrum antimicrobial peptide resistance by MprF-mediated aminoacylation and flipping of phosphorlipids. Molecul Microbiol, 2011, 80(2): 290-299.

[29] Peschel A, Jack R W, Otto M et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. Exp Med, 2001,193(9):1067-1076.

[30] Ernst C M, Staubitz P, Mishra N N, et al. The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog, 2009,5 (11): e1000660.

[31] Moon K, Gottesman S. A PhoQ/P-regulated small RNA regulates sensitivity of Escherichia coli to antimicrobial peptides. Mol Microbiol, 2009, 74(6):1314-1330.

[32] Herrera C M, Hankins J V, Trent S. Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides. Mol Microbiol, 2010, 76(6): 1444-1460.

[33] Zhou Z M, Ribeiro A A, Lin S H, et al. Lipid A Modifications in Polymyxin-resistant Salmonella typhimurium PMRA-dependent 4-amino-4-deoxy-l-arabinose, and phosphorethanolamine incorporation. J Biol Chem, 2001, 276(46):43111-43121.

[34] Raetz C R, Reynolds C M, Trent M S, et al. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem, 2007, 76: 295-329.

[35] Campos M A, Vargas M A, Regueiro V, et al. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun, 2004, 72(12): 7107-7114.

[36] Jin T, Bokarewa M, Tarkowski A. The role of urokinase in innate immunity against Staphylococcus aureus. Microbes Infect, 2005,7(9-10): 1170-1175.

[37] Llobet E, Tomás J M, Bengoechea J A. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology, 2008, 154(Pt 12):3877-3886.

[38] Bader M W, Navarre W W, Shiau W, et al. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Mol Microbiol, 2003,50(1):219-230.

[39] Sieprawska-Lupa M, Mydel P, Krawczyk K, et al. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother, 2004, 48(12): 4673-4679

[40] Nyberg P, Rasmussen M, Björck L. Alpha-2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37. J Biol Chem, 2004,279(51): 52820-52823.

[41] Johansson L, Thulin P, Sendi P, et al. Cathelicidin LL-37 in severe Streptococcus pyogenes soft tissue infections in humans. Infect Immun, 2008,76(8):3399-3404.

[42] Karlsson C, Andersson M L, Collin M, et al. SufA——a novel subtilisinlike serine proteinase of Finegoldia magna. Microbiology, 2007, 153: 4208-4218.

[43] Schmidtchen A, Frick I M, Andersson E, et al. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol, 2002,46(1):157-168.

[44] Meiller T F, Hube B, Schild L, et al. A novel immune evasion strategy of Candida albicans: proteolytic cleavage of a salivary antimicrobial peptide. PLoS One, 2009,4(4):e5039.

[45] Vincents B, Onnerfjord P, Gruca M, et al. Down-regulation of human extracellular cysteine protease inhibitors by the secreted staphylococcal cysteine proteases, staphopain A and B. J Biol Chem, 2007,388(4): 437-446.

[46] Potempa J, Pike R N. Corruption of innate immunity by bacterial proteases. J Innate Immun, 2009,1(2):70-87.

[47] Lai Y, Villaruz A E, Li M, et al. The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in Staphylococci. Mol Microbiol, 2007, 63(2):497 -506.

[48] Giuliani A, Rinaldi A C. Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches.Cell Mol Life Sci,2011,68(13):2255-2266.

[49] Davis J, Davies D. Origin and evolution of antibiotic resistance. Microbiol Mol Biol Rev, 2010,74(3): 417-433.

[50] Putman M, van Veen H W, Konings W N. Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev, 2000,64(4):672-693.

[51] Davidson A L, Dassa E, Orelle C, et al. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev, 2008,72(2): 317-364.

[52] Davidson A L, Maloney P C. ABC transporters: how small machines do a big job. Trends Microbiol, 2007, 15(10):448-455.

[53] Boumendjel A, Boutonnat J, Robert J. ABC transporters and multidrug resistance. New Jersey: John Wiley & Sons, 2009: 184-195.

[54] Seeger M A, van Veen H W. Molecular basis of multidrug transport by ABC transporters. Biochim Biophys Acta, 2009(5), 1794: 725-737.

[55] Linton K J. Structure and function of ABC transporters. Physiol, 2007, 22(2): 122-130.

[56] Collins B, Curtis N, Cotter P D, et al. The ABC transporter AnrAB contributes to the innate resistance of Listeria monocytogenes to Nisin, Bacitracin, and various β-Lactam Antibiotics. Antimicrob Agents Chemother, 2010,54(10):4416-4423.

[57] Dintner S, Staron, Berchtold E, et al. Coevolution of ABC transporters and two-component regulatory systems as resistance modules against antimicrobial peptides in Firmicutes Bacteria. Bacteriol, 2011, 193(15): 3851-3862.

[58] Vardy E, Arkin I T, Gottschalk K E, et al. Structural conservation in the major facilitator superfamily as revealed by comparative modeling. Prot Sci, 2004, 13(7):1832-1840.

[59] Law C J, Maloney P C, Wang D N. Ins and outs of major facilitator superfamily antiporters. Annu Rev Microbiol, 2008, 62: 289-305.

[60] Fluman N, Bibi E. Bacterial multidrug transport through the lens of the major facilityator superfamily. Biochim Biophys Acta, 2009, 1794(5): 738-747.

[61] Saier M H, Beatty J T, Goffeau A, et al. The major facilitator superfamily. Mol Mcirobiol Biotechnol, 1999,1(2): 257-279.

[62] Brogden K A, Chris Mininon K F, Cornick N, et al. Virulence mechanisms of bacterial pathogens. Third Edition. Washington: American Society for Microbiology Press, 2007. 32-33.

[63] Nikaido H. Multidrug efflux pumps of gram-negative bacteria. Bacteriol, 1996, 178(20):5853-5859.

[64] Takatsuka Y, Chen C, Nikaido H. Mechanism of recognition of compounds of diverse structures by the multidrug efflux pumps AcrB of Escherichia coli. Proc Nat Acad Sci U S A, 2010, 107(15): 6559-6565.

[65] Murakami S. Multidrug efflux transporter, AcrB-the pumping mechanism. Curr Opin Struct Biol, 2008, 18(4): 459-465.

[66] Misra R, Bavro V N. Assembly and transport mechanism of tripartite drug efflux systems. Biochim Biophys Acta, 2009, 1794(5): 817-825.

[67] Bay D C, Rommens K L, Turner R J. Small multidrug resistance proteins: a multidrug transporter family that continues to grow. Biochim Biophys Acta, 2008, 1778(9): 1814-1838.

[68] Paulsen I T, Skurray R A, Tam R, et al. The SMR family: a novel family of multidrug efflux proteins involved with the efflux of lipophilic drugs. Mol Microbiol 1996, 19(6):1167-1175.

[69] Kolbusz M A, Horst R, Slotboom D J, et al. Orientation of small multidrug resistance transporter subunits in the membrane: correlateion with the positive-inside rule. Mol Biol, 2010,402: 127-138.

[70] Bay D, Turner R J. Diversity and evolution of the small multidrug resistance protein family. BMC Evolut Biol, 2009,9:140.

[71] Kuroda T, Tsuchiya. Multidrug efflux transporters in the MATE family. Biochim Biophys Acta, 2009,1794(5): 763-768.

[72] Morita Y, Kodama K, Shiota S, et al. NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Escherichia coli. Antimicrob Agents Chemother, 1998, 42(7): 1778-1782.

[73] Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie, 2005, 87(12): 1137-1147.

[74] Pagès J M, Amaral L. Mechanisms of drug efflux and strategies to combat them: Challenging the efflux pump of Gram-negative bacteria. Biochim Biophys Acta, 2009,1794(5):826-833.

[75] Pagès J M, Sandrine A F, Mahamoud A, et al. Efflux pumps of gram-negative bacteria, a new target for new molecules. Curr Top Med Chem, 2010,10(18): 1848-1857.

[76] Askoura M, Mottawea W, Abujamel T, et al. Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa. Libyan J Med, 2011, 6:5870.

[77] Lubelski J, Konings W N, Driessen A J M. Distribution and physiology of ABC-type transporters contributing to multi-drug resistance in Bacteria. Microbiol Mol Biol Rev, 2007,71(3): 463-476.

[78] Ejim L, Farha M A, Falconer S B, et al. Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat Chem Biol, 2011, 7(6):348-350.

[79] Hammami R, Fliss I. Current trends in antimicrobial agent research: chemo- and bioinformatics approaches. Drug Discov Today, 2010, 15(13-14): 540-546.

[80] Handelsman J. Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Bio Rev, 2004, 68(4): 669-685.

[81] Wong H L, Chattopadhyay N, Wu X Y, et al. Naontechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev, 2010, 62(4-5): 503-517.

[1] 马巧妮,王萌,朱兴全. 重组酶介导扩增技术及其在病原微生物快速检测中的应用进展*[J]. 中国生物工程杂志, 2021, 41(6): 45-49.
[2] 邓蕊,曾佳利,卢雪梅. 基于Musca domestica cecropin的抗肿瘤小分子衍生肽筛选及构效关系解析*[J]. 中国生物工程杂志, 2021, 41(11): 14-22.
[3] 唐馨,毛新芳,马彬云,苟萍. 抗菌肽的研究现状和挑战 *[J]. 中国生物工程杂志, 2019, 39(8): 86-94.
[4] 杨隆兵,国果,马慧玲,李妍,赵欣宇,苏佩佩,张勇. 家蝇抗菌肽AMPs17蛋白原核表达条件的优化及其抗真菌活性检测 *[J]. 中国生物工程杂志, 2019, 39(4): 24-31.
[5] 唐健雪,肖永乐,彭俊杰,赵世纪,万小平,高荣. 融合抗菌肽基因在重组毕赤酵母的表达及体外活性研究 *[J]. 中国生物工程杂志, 2018, 38(6): 9-16.
[6] 杨静,贾如涵,李文慧,石大林,邵明洋,韩跃武. 抗菌肽改良设计及抗炎作用的研究进展[J]. 中国生物工程杂志, 2018, 38(1): 57-61.
[7] 温赛, 刘怀然, 韩煦, 李天, 邢旋. 综述人工合成型抗菌肽及其药学应用研究进展[J]. 中国生物工程杂志, 2016, 36(8): 89-98.
[8] 刘晓明, 姜宁, 张爱忠, 蔡鹏. 杂合抗菌肽在毕赤酵母中的表达及其活性测定[J]. 中国生物工程杂志, 2016, 36(2): 81-89.
[9] 巫春旭, 卢雪梅, 金小宝, 朱家勇. 天蚕素类抗菌肽分子设计研究进展[J]. 中国生物工程杂志, 2016, 36(2): 96-100.
[10] 陈洁梅, 张灿辉, 艾田. 解淀粉芽孢杆菌KN-BL-1及其发酵豆粕产抗菌肽类物质的研究[J]. 中国生物工程杂志, 2014, 34(10): 61-66.
[11] 武如娟, 张日俊. 杂合抗菌肽设计及生物学活性的研究进展[J]. 中国生物工程杂志, 2013, 33(9): 94-100.
[12] 陈宇婷, 王长海, 严秀文, 黎军胜. 抗菌肽的设计及其应用[J]. 中国生物工程杂志, 2013, 33(7): 97-102.
[13] 明飞平, 杨军, 朱进美, 邝哲师, 李华周, 夏枫耿, 叶明强, 王候光, 赵祥杰, 黄志丰, 蔡海明, 施巨清, 马苗鹏, 张玲华. 5’非翻译区序列改建提高抗菌肽PR39表达[J]. 中国生物工程杂志, 2013, 33(12): 86-91.
[14] 舒梅, 许杨, 徐熙, 涂追. 两种水生动物抗菌肽的原核表达及活性分析[J]. 中国生物工程杂志, 2011, 31(02): 56-61.
[15] 李朴,文阳安,刘靳波,扬细媚,周金敬,涂植光. 抗菌肽Bactenecin7重组质粒构建及其在乳酸菌的分泌表达和活性鉴定[J]. 中国生物工程杂志, 2009, 29(01): 70-74.