Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2018, Vol. 38 Issue (6): 86-94    DOI: 10.13523/j.cb.20180612
综述     
革兰氏阳性菌脂蛋白的研究进展 *
吴小芳,刘家亨,熊慧,乔建军,朱宏吉()
天津大学化工学院 系统生物工程教育部重点实验室 天津化学化工协同创新中心合成生物学平台 天津 300072
Research Progress of Lipoprotein in Gram-positive Bacteria
Xiao-fang WU,Jia-heng LIU,Hui XIONG,Jian-jun QIAO,Hong-ji ZHU()
School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering of Ministry of Education, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072, China
 全文: PDF(1303 KB)   HTML
摘要：

细菌脂蛋白是细胞膜的重要组成部分,对细菌发挥各种生理活性起重要作用,与营养摄取、环境感知、细胞膜和细胞壁稳态的维持、蛋白质的折叠和定位等过程密切相关。随着生物技术不断发展和完善,越来越多的脂蛋白种类及功能被发现。综述了革兰氏阳性菌中脂蛋白的功能、生物合成过程和应用方面的研究进展,重点介绍了脂蛋白生物合成过程中关键酶磷脂酰甘油转移酶(Lipoprotein diacylglyceryl transferase,Lgt)和脂蛋白信号肽酶(Lipoprotein signal peptidase II,LspA)对革兰氏阳性菌生理活性产生的影响,为今后革兰氏阳性菌脂蛋白的研究提出了展望和建议。
关键词： 脂蛋白;  革兰氏阳性菌;  疫苗;  Lgt;  LspA    
Abstract:

As important components of cell membrane,bacterial lipoproteins play critical roles in many physiological process of bacteria, such as nutrient acquisition, environmental sensing, maintaining cell envelope and cell wall stability and electron transfer. With the continuous development and improvement of biotechnology, more and more lipoprotein as well as their functions have been discovered. This paper reviews the research progress of lipoprotein functions, biosynthesis and applications in Gram-positive bacteria. The influence of Lgt and LspA, key enzymes in lipoprotein biosynthesis, on physiological activity of Gram-positive bacteria is also addressed. Finally, the prospect and suggestion are provided for the future research on Gram-positive bacteria lipoproteins.
Key words: Lipoprotein    Gram-positive bacteria    Vaccine    Lgt    LspA
收稿日期: 2018-03-09 出版日期: 2018-07-06
ZTFLH:  Q935  
基金资助: * 国家自然科学基金资助项目(31570089)
通讯作者: 朱宏吉     E-mail: zhj@tju.edu.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　　
吴小芳
刘家亨
熊慧
乔建军
朱宏吉

引用本文:

吴小芳,刘家亨,熊慧,乔建军,朱宏吉. 革兰氏阳性菌脂蛋白的研究进展 *[J]. 中国生物工程杂志, 2018, 38(6): 86-94.

Xiao-fang WU,Jia-heng LIU,Hui XIONG,Jian-jun QIAO,Hong-ji ZHU. Research Progress of Lipoprotein in Gram-positive Bacteria. China Biotechnology, 2018, 38(6): 86-94.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20180612    或    https://manu60.magtech.com.cn/biotech/CN/Y2018/V38/I6/86

图1  脂蛋白的生物合成过程
图2  成熟脂蛋白和未完全修饰脂蛋白前体与细胞膜的结合
物种 突变基因 表型 参考文献
Mycobacterium tuberculosis lspA 毒力明显降低;在小鼠巨噬细胞中的增殖能力降低;在小鼠脾脏细胞内的生长能力降低。 [47]
Mycobacterium bovis lspA 外周血单核细胞CD4+T细胞中HIV病毒的传染性降低 [48]
Clostridium difficile lgt 产孢能力下降 [49]
Staphylococcus aureus lgt 在营养丰富的培养基中正常生长,但在营养成分不足的培养基中生长受限;侵染人体单核细胞、上皮细胞、内皮后,细胞促炎症因子分泌减少 [42]
lgt 对C57BL/6脓毒症小鼠的致病性降低 [50]
lgt 在血液或激活的巨噬细胞中生长受限;菌体的免疫反应无法激活;逃避宿主免疫系统识别,毒力增强 [51]
lgt 影响脂蛋白与细胞膜的共价连接;导致脂蛋白在培养基中积累 [52]
lgt 不能诱导产生IL-8;抑制菌体刺激IL-6等的能力;TLR2介导的免疫激活反应受到影响 [53]
lspA 毒力减弱 [54-55]
Streptococcus agalactiae lgt 生长能力不受影响;氧耐受能力下降;细胞膜组成发生变化;对胎儿内皮细胞的粘附作用降低 [56]
lgt 生长变慢;对小鼠细胞毒力增强;不能通过释放脂蛋白与TLR2相互作用来激活免疫反应 [57]
lspA 生长变慢;不能通过TLR2激活免疫反应
Streptococcus pneumoniae lgt 生存能力降低 [58]
lspA 影响了在动物细胞中的毒力;氧耐受能力降低;在人类血液中的生存能力降低 [59]
Streptococcus gordonii lgt 无法通过TLR2激活反应来诱导人体PDL细胞中IL-8的产生 [60]
lgt 不能正常表达iNOS;TLR2介导的免疫激活反应受到影响 [61]
Listeria monocytogenes lgt 生长略微减慢;对阳离子肽的敏感性增加; TLR2介导的免疫激活反应受到影响;对小鼠细胞毒力减弱 [62-63]
lspA 在巨噬细胞中生长减慢,吞噬体逃逸;毒力减弱 [64]
Enterococcus faecalis lgt 影响生长;毒力减弱 [65]
Bacillus anthracis lgt 影响产孢;毒力减弱 [66]
Lactococcus lactis lspA 不影响菌体的生长;产生带有信号肽的脂蛋白前体,但是不影响其功能,如PrtM和OppA [44]
Streptomyces coelicolor lgt 不影响菌体的形态和生长 [67]
lspA 影响了菌体生长和孢子形成;影响脂蛋白对细胞膜的锚定
Streptococcus mutans lgt 影响脂蛋白MsmE的定位,且与培养条件有关 [68]
lspA 影响了脂蛋白在细胞膜上的锚定及功能
表1  革兰氏阳性菌Lgt或LspA突变菌的表型
[1] Hantke K, Braun V . Covalent binding of lipid to protein. The FEBS Journal, 1973,34(2):284-296.
doi: 10.1111/j.1432-1033.1973.tb02757.x
[2] Braun V, Wu H C . Lipoproteins, structure, function, biosynthesis and model for protein export. New Comprehensive Biochemistry. 1994,27:319-341.
doi: 10.1016/S0167-7306(08)60417-2
[3] Von H G . The structure of signal peptides from bacterial lipoproteins. Protein Engineering, Design and Selection, 1989,2(7):531-534.
doi: 10.1093/protein/2.7.531 pmid: 2664762
[4] Sutcliffe I C, Russell R R . Lipoproteins of gram-positive bacteria. Journal of Bacteriology, 1995,177(5):1123.
doi: 10.1111/j.1365-2672.1995.tb05033.x pmid: 176714
[5] Kovacs-Simon A, Titball R W, Michell S L . Lipoproteins of bacterial pathogens. Infection and Immunity, 2011,79(2):548-561.
doi: 10.1128/IAI.00682-10
[6] Sutcliffe I C, Hutchings M I . Putative lipoproteins identified by bioinformatic genome analysis of Leifsonia xyli ssp. xyli, the causative agent of sugarcane ratoon stunting disease. Molecular Plant Pathology, 2007,8(1):121-128.
doi: 10.1111/j.1364-3703.2006.00377.x pmid: 20507484
[7] Babu M M, Priya M L, Selvan A T , et al. A database of bacterial lipoproteins (DOLOP) with functional assignments to predicted lipoproteins. Journal of Bacteriology, 2006,188(8):2761-2773.
doi: 10.1128/JB.188.8.2761-2773.2006 pmid: 16585737
[8] Sutcliffe I C, Harrington D J . Lipoproteins of Mycobacterium tuberculosis:an abundant and functionally diverse class of cell envelope components. FEMS Microbiology Reviews, 2004,28(5):645-659.
doi: 10.1016/j.femsre.2004.06.002 pmid: 256148
[9] Hutchings M I, Palmer T, Harrington D J , et al. Lipoprotein biogenesis in Gram-positive bacteria:knowing when to hold ’em, knowing when to fold ’em. Trends in Microbiology, 2009,17(1):13-21.
doi: 10.1016/j.tim.2008.10.001 pmid: 19059780
[10] Biemans-Oldehinkel E, Doeven M K, Poolman B . ABC transporter architecture and regulatory roles of accessory domains. FEBS Letters, 2006,580(4):1023-1035.
doi: 10.1016/j.febslet.2005.11.079 pmid: 16375896
[11] Davidson A L, Dassa E, Orelle C , et al. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiology and Molecular Biology Reviews, 2008,72(2):317-364.
doi: 10.1128/MMBR.00031-07 pmid: 18535149
[12] Tam R, Saier M H . Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiological Reviews, 1993,57(2):320-346.
[13] Claverys J P . A new family of high-affinity ABC manganese and zinc permeases. Research in Microbiology, 2001,152(34):231-243.
doi: 10.1016/S0923-2508(01)01195-0 pmid: 11421271
[14] Deka R K, Brautigam C A, Yang X F , et al. The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in Treponema pallidum. Journal of Biological Chemistry, 2006,281(12):8072-8081.
doi: 10.1074/jbc.M511405200 pmid: 16418175
[15] Liu J, Zhou J, Wang L , et al. Improving nitrogen source utilization from defatted soybean meal for nisin production by enhancing proteolytic function of Lactococcus lactis F44. Scientific Reports, 2017,7(1):6189.
doi: 10.1038/s41598-017-06537-w pmid: 28733629
[16] Claverys J P, Grossiord B, Alloing G . Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in sensing environmental conditions? Research in Microbiology, 2000,151(6):457-463.
doi: 10.1016/S0923-2508(00)00169-8 pmid: 10961459
[17] Chandler J R, Dunny G M . Enterococcal peptide sex pheromones:synthesis and control of biological activity. Peptides, 2004,25(9):1377-1388.
doi: 10.1016/j.peptides.2003.10.020 pmid: 15374642
[18] Clewell D B, An F Y, Flannagan S E , et al. Enterococcal sex pheromone precursors are part of signal sequences for surface lipoproteins. Molecular Microbiology, 2000,35(1):246-247.
doi: 10.1046/j.1365-2958.2000.01687.x pmid: 10632894
[19] Igarashi T, Setlow B, Paidhungat M , et al. Effects of a gerF (Lgt) mutation on the germination of spores of Bacillus subtilis. Journal of Bacteriology, 2004,186(10):2984-2991.
doi: 10.1128/JB.186.10.2984-2991.2004 pmid: 400631
[20] Pelczar P L, Igarashi T, Setlow B , et al. Role of GerD in germination of Bacillus subtilis spores. Journal of Bacteriology, 2007,189(3):1090-1098.
doi: 10.1128/JB.01606-06 pmid: 17122337
[21] 刘朝, 乔建军, 朱宏吉 . 乳酸菌肽聚糖的研究进展. 微生物学通报, 2016,43(1):188-197.
doi: 10.13344/j.microbiol.china.150222
Liu Z, Qiao J J, Zhu H J . Research progress in peptidoglycan of lactic acid bacteria. Microbiology China, 2016,43(1):188-197.
doi: 10.13344/j.microbiol.china.150222
[22] Biarrotte-Sorin S, Hugonnet J E, Delfosse V , et al. Crystal structure of a novel β-lactam-insensitive peptidoglycan transpeptidase. Journal of Molecular Biology, 2006,359(3):533-538.
doi: 10.1016/j.jmb.2006.03.014 pmid: 16647082
[23] Lavollay M, Arthur M, Fourgeaud M , et al. The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L, D-transpeptidation. Journal of Bacteriology, 2008,190(12):4360-4366.
doi: 10.1128/JB.00239-08 pmid: 2446752
[24] Marraffini L A , DeDent A C, Schneewind O . Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiology and Molecular Biology Reviews, 2006,70(1):192-221.
doi: 10.1128/MMBR.70.1.192-221.2006 pmid: 1393253
[25] Kontinen V P, Sarvas M . The PrsA lipoprotein is essential for protein secretion in Bacillus subtilis and sets a limit for high-level secretion. Molecular Microbiology, 1993,8(4):727-737.
doi: 10.1111/j.1365-2958.1993.tb01616.x pmid: 8332065
[26] Pahl A, Keller U . Streptomyces chrysomallus FKBP-33 is a novel immunophilin consisting of two FK506 binding domains; its gene is transcriptionally coupled to the FKBP-12 gene. The EMBO Journal, 1994,13(15):3472-3480.
doi: 10.1002/j.1460-2075.1994.tb06653.x pmid: 8062824
[27] Hermans P W M, Adrian P V, Albert C , et al. The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization. Journal of Biological Chemistry, 2006,281(2):968-976.
doi: 10.1074/jbc.M510014200
[28] Serek J, Bauer-Manz G, Struhalla G , et al. Escherichia coli YidC is a membrane insertase for Sec-independent proteins. The EMBO Journal, 2004,23(2):294-301.
doi: 10.1038/sj.emboj.7600063
[29] Heras B, Kurz M, Jarrott R , et al. Staphylococcus aureus dsba does not have a destabilizing disulfide a new paradigm for bacterial oxidative folding. Journal of Biological Chemistry, 2008,283(7):4261-4271.
doi: 10.1074/jbc.M707838200
[30] Ganeshkumar N, Song M , McBride B C . Cloning of a Streptococcus sanguis adhesin which mediates binding to saliva-coated hydroxyapatite. Infection and Immunity, 1988,56(5):1150-1157.
[31] Zheng F, Shao Z Q, Hao X , et al. Identification of oligopeptide-binding protein (OppA) and its role in the virulence of Streptococcus suis serotype 2. Microbial Pathogenesis, 2018,118:322-329.
doi: 10.1016/j.micpath.2018.03.061
[32] Nguyen M T, Uebele J, Kumari N , et al. Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses. Nature Communications, 2017,8(1):2246.
doi: 10.1038/s41467-017-02234-4 pmid: 29269769
[33] Nguyen M T, Götz F . Lipoproteins of Gram-positive bacteria:key players in the immune response and virulence. Microbiology and Molecular Biology Reviews, 2016,80(3):891-903.
doi: 10.1128/MMBR.00028-16 pmid: 27512100
[34] Buddelmeijer N . The molecular mechanism of bacterial lipoprotein modification-How, when and why? FEMS Microbiology Reviews, 2015,39(2):246-261.
doi: 10.1093/femsre/fuu006 pmid: 25670733
[35] Vogeley L, El Arnaout T, Bailey J , et al. Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin. Science, 2016,351(6275):876-880.
doi: 10.1126/science.aad3747 pmid: 26912896
[36] Narita S, Tokuda H . Bacterial lipoproteins; biogenesis, sorting and quality control. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2016,1862:1414-1423.
doi: 10.1016/j.bbalip.2016.11.009 pmid: 27871940
[37] Nakayama H, Kurokawa K, Lee B L . Lipoproteins in bacteria:structures and biosynthetic pathways. The FEBS Journal, 2012,279(23):4247-4268.
doi: 10.1111/febs.12041 pmid: 23094979
[38] Kumari N, Götz F, Nguyen M T . Aspartate tightens the anchoring of staphylococcal lipoproteins to the cytoplasmic membrane. MicrobiologyOpen, 2017,6(Pt9):e00525.
doi: 10.1002/mbo3.525 pmid: 28901671
[39] Robichon C, Vidal-Ingigliardi D, Pugsley A P . Depletion of apolipoprotein N-acyltransferase causes mislocalization of outer membrane lipoproteins in Escherichia coli. Journal of Biological Chemistry, 2005,280(2):974-983.
doi: 10.1074/jbc.M411059200
[40] Sankaran K, Gupta S D, Wu H C . Modification of bacterial lipoproteins, Methods in Enzymology, 1995,250:683-697.
doi: 10.1016/0076-6879(95)50105-3
[41] Baumgärtner M, Kärst U, Gerstel B , et al. Inactivation of Lgt allows systematic characterization of lipoproteins from Listeria monocytogenes. Journal of Bacteriology, 2007,189(2):313-324.
doi: 10.1128/JB.00976-06 pmid: 456474
[42] Stoll H, Dengjel J, Nerz C , et al. Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation. Infection and Immunity, 2005,73(4):2411-2423.
doi: 10.1128/IAI.73.4.2411-2423.2005 pmid: 15784587
[43] Malinverni J C, Werner J, Kim S , et al. YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli. Molecular Microbiology, 2006,61(1):151-164.
doi: 10.1111/j.1365-2958.2006.05211.x pmid: 16824102
[44] Venema R , Tjalsma H, van Dijl J M , et al. Active lipoprotein precursors in the gram-positive eubacterium Lactococcus lactis. Journal of Biological Chemistry, 2003,278(17):14739-14746.
doi: 10.1074/jbc.M209857200 pmid: 12584195
[45] Leskelä S, Wahlström E, Kontinen V P , et al. Lipid modification of prelipoproteins is dispensable for growth but essential for efficient protein secretion in Bacillus subtilis:characterization of the Lgt gene. Molecular Microbiology, 1999,31(4):1075-1085.
doi: 10.1046/j.1365-2958.1999.01247.x pmid: 10096076
[46] Tjalsma H, Kontinen V P, Prágai Z , et al. The role of lipoprotein processing by signal peptidase II in the gram-positive eubacterium Bacillus subtilis signal peptidase II is required for the efficient secretion of α-amylase, a non-lipoprotein. Journal of Biological Chemistry, 1999,274(3):1698-1707.
doi: 10.1074/jbc.274.3.1698
[47] Sander P, Rezwan M, Walker B , et al. Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. Molecular Microbiology, 2004,52(6):1543-1552.
doi: 10.1111/j.1365-2958.2004.04041.x pmid: 15186407
[48] Skerry C, Klinkenberg L G, Page K R , et al. TLR2-modulating lipoproteins of the Mycobacterium tuberculosis complex enhance the HIV infectivity of CD4+ T cells. PloS One, 2016,11(1):e0147192.
doi: 10.1371/journal.pone.0147192 pmid: 4725761
[49] Charlton T M, Kovacs-Simon A, Michell S L , et al. Quantitative lipoproteomics in clostridium difficile reveals a role for lipoproteins in sporulation. Chemistry & Biology, 2015,22(11):1562-1573.
doi: 10.1016/j.chembiol.2015.10.006 pmid: 26584780
[50] Schmaler M, Jann N J, Ferracin F , et al. Lipoproteins in Staphylococcus aureus mediate inflammation by TLR2 and iron-dependent growth in vivo. The Journal of Immunology, 2009,182(11):7110-7118.
doi: 10.4049/jimmunol.0804292 pmid: 19454708
[51] Wardenburg J B, Williams W A, Missiakas D . Host defenses against Staphylococcus aureus infection require recognition of bacterial lipoproteins. Proceedings of the National Academy of Sciences, 2006,103(37):13831-13836.
doi: 10.1073/pnas.0603072103 pmid: 16954184
[52] Graf A, Lewis R J, Fuchs S , et al. The hidden lipoproteome of Staphylococcus aureus. International Journal of Medical Microbiology, 2018.
[53] Hanzelmann D, Joo H S, Franz-Wachtel M , et al. Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants. Nature Communications, 2016,7:12304.
doi: 10.1038/ncomms12304 pmid: 2974
[54] Coulter S N, Schwan W R , Ng E Y W , et al. Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments. Molecular Microbiology, 1998,30(2):393-404.
doi: 10.1046/j.1365-2958.1998.01075.x pmid: 9791183
[55] Mei J M, Nourbakhsh F, Ford C W , et al. Identification of Staphylococcus aureus virulence genes in a murine model of bacteraemia using signature-tagged mutagenesis. Molecular Microbiology, 1997,26(2):399-407.
doi: 10.1046/j.1365-2958.1997.5911966.x pmid: 9383163
[56] Bray B A, Sutcliffe I C, Harrington D J . Impact of Lgt mutation on lipoprotein biosynthesis and in vitro phenotypes of Streptococcus agalactiae. Microbiology, 2009,155(5):1451-1458.
doi: 10.1099/mic.0.025213-0 pmid: 19383708
[57] Henneke P, Dramsi S, Mancuso G , et al. Lipoproteins are critical TLR2 activating toxins in group B streptococcal sepsis. The Journal of Immunology, 2008,180(9):6149-6158.
doi: 10.4049/jimmunol.0990005 pmid: 18424736
[58] Petit C M, Brown J R, Ingraham K , et al. Lipid modification of prelipoproteins is dispensable for growth in vitro but essential for virulence in Streptococcus pneumoniae. FEMS Microbiology Letters, 2001,200(2):229-233.
doi: 10.1016/S0378-1097(01)00233-6 pmid: 11425480
[59] Khandavilli S, Homer K A, Yuste J , et al. Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase is required for ABC transporter function and full virulence. Molecular Microbiology, 2008,67(3):541-557.
doi: 10.1111/j.1365-2958.2007.06065.x pmid: 18086214
[60] Kim A R, Ahn K B, Kim H Y , et al. Streptococcus gordonii lipoproteins induce IL-8 in human periodontal ligament cells. Molecular Immunology, 2017,91:218-224.
doi: 10.1016/j.molimm.2017.09.009
[61] Kim H Y, Baik J E, Ahn K B , et al. Streptococcus gordonii induces nitric oxide production through its lipoproteins stimulating Toll-like receptor 2 in murine macrophages. Molecular Immunology, 2017,82:75-83.
doi: 10.1016/j.molimm.2016.12.016 pmid: 28038357
[62] Baumgärtner M, Kärst U, Gerstel B , et al. Inactivation of Lgt allows systematic characterization of lipoproteins from Listeria monocytogenes. Journal of Bacteriology, 2007,189(2):313-324.
doi: 10.1128/JB.00976-06 pmid: 456474
[63] Machata S, Tchatalbachev S, Mohamed W , et al. Lipoproteins of Listeria monocytogenes are critical for virulence and TLR2-mediated immune activation. The Journal of Immunology, 2008,181(3):2028-2035.
doi: 10.4049/jimmunol.181.3.2028 pmid: 18641340
[64] Réglier-Poupet H, Frehel C, Dubail I , et al. Maturation of lipoproteins by type II signal peptidase is required for phagosomal escape of Listeria monocytogenes. Journal of Biological Chemistry, 2003,278(49):49469-49477.
doi: 10.1074/jbc.M307953200 pmid: 12975369
[65] Reffuveille F, Serror P, Chevalier S , et al. The prolipoprotein diacylglyceryl transferase (Lgt) of Enterococcus faecalis contributes to virulence. Microbiology, 2012,158(3):816-825.
doi: 10.1099/mic.0.055319-0 pmid: 22135097
[66] Okugawa S, Moayeri M, Pomerantsev A P , et al. Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis. Molecular Microbiology, 2012,83(1):96-109.
doi: 10.1111/j.1365-2958.2011.07915.x pmid: 22103323
[67] Thompson B J, Widdick D A, Hicks M G , et al. Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor. Molecular Microbiology, 2010,77(4):943-957.
[68] Arimoto T, Igarashi T . Role of prolipoprotein diacylglyceryl transferase (Lgt) and lipoprotein-specific signal peptidase II (LspA) in localization and physiological function of lipoprotein MsmE in Streptococcus mutans. Molecular Oral Microbiology, 2008,23(6):515-519.
doi: 10.1111/j.1399-302X.2008.00455.x pmid: 18954360
[69] Bartual S G, Alcorlo M, Martínez-Caballero S , et al. Three-dimensional structures of Lipoproteins from Streptococcus pneumoniae and Staphylococcus aureus. International Journal of Medical Microbiology, 2017.
[70] Sigal L H, Zahradnik J M, Lavin P , et al. A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. New England Journal of Medicine, 1998,339(4):216-222.
doi: 10.1056/NEJM199807233390402
[71] 陈国忠, 张燕娇, 陈师勇 . 革兰氏阴性菌脂蛋白Lol系统转运蛋白的功能及表面展示分泌机制. 微生物学报, 2017,57(12):1769-1777.
Chen G Z, Zhang Y J, Chen S Y . Functions of Lol system proteins and surface-exposed mechanisms of lipoproteins in gram-negative bacteria. Acta Microbiologica Sinica, 2017,57(12):1769-1777.
[72] Foster T J, Geoghegan J A, Ganesh V K , et al. Adhesion, invasion and evasion:the many functions of the surface proteins of Staphylococcus aureus. Nature Reviews Microbiology, 2014,12(1):49.
doi: 10.1038/nrmicro3161 pmid: 24336184
[73] Kehl-Fie T E, Zhang Y, Moore J L , et al. MntABC and MntH contribute to systemic Staphylococcus aureus infection by competing with calprotectin for nutrient manganese. Infection and Immunity, 2013,81(9):3395-3405.
doi: 10.1128/IAI.00420-13
[74] Anderson A S, Scully I L, Timofeyeva Y , et al. Staphylococcus aureus manganese transport protein C is a highly conserved cell surface protein that elicits protective immunity against S. aureus and Staphylococcus epidermidis. The Journal of Infectious Diseases, 2012,205(11):1688-1696.
doi: 10.1093/infdis/jis272 pmid: 3348682
[75] Mariotti P, Malito E, Biancucci M , et al. Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochemical Journal, 2013,449(3):683-693.
doi: 10.1042/BJ20121426 pmid: 23113737
[76] Podkowa K J , Briere L A K, Heinrichs D E , et al. Crystal and solution structure analysis of FhuD2 from Staphylococcus aureus in multiple unliganded conformations and bound to ferrioxamine-B. Biochemistry, 2014,53(12):2017-2031.
doi: 10.1021/bi401349d pmid: 24606332
[77] Mishra R P N, Mariotti P, Fiaschi L , et al. Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. The Journal of Infectious Diseases, 2012,206(7):1041-1049.
doi: 10.1093/infdis/jis463 pmid: 22829645
[78] Koponen O, Takala T M, Saarela U , et al. Distribution of the NisI immunity protein and enhancement of nisin activity by the lipid-free NisI. FEMS Microbiology Letters, 2004,231(1):85-90.
doi: 10.1016/S0378-1097(03)00934-0 pmid: 14769471
[79] Takala T M, Koponen O, Qiao M , et al. Lipid-free NisI:Interaction with nisin and contribution to nisin immunity via secretion. FEMS Microbiology Letters, 2004,237(1):171-177.
doi: 10.1016/j.femsle.2004.06.032
[1] 郑婕,吴昊,乔建军,朱宏吉. 革兰氏阳性菌荚膜多糖研究进展*[J]. 中国生物工程杂志, 2021, 41(7): 91-98.
[2] 肖云喜,张俊河,杨雯雯,程洪伟. 用于疫苗生产的人二倍体细胞研究进展*[J]. 中国生物工程杂志, 2021, 41(11): 74-81.
[3] 朱潇静,王芮,张欣欣,靳家鑫,路闻龙,丁大顺,霍翠梅,李青梅,孙爱军,庄国庆. 利用细菌人工染色体技术构建整合F基因的重组MDV疫苗株*[J]. 中国生物工程杂志, 2021, 41(10): 33-41.
[4] 程旭,杨雨睛,吴赛男,侯勤龙,李咏梅,韩慧明. 金黄色葡萄球菌SarA、IcaA及其融合基因的DNA疫苗构建及在小鼠免疫应答中的初步研究 *[J]. 中国生物工程杂志, 2020, 40(7): 41-50.
[5] 刘珍珍,田大勇. 狂犬病疫苗蔗糖密度梯度离心纯化工艺开发 *[J]. 中国生物工程杂志, 2020, 40(4): 25-33.
[6] 钱颖,钱晨,白晓庆,王晶晶. 免疫佐剂在肿瘤免疫疗法中的应用进展 *[J]. 中国生物工程杂志, 2020, 40(3): 96-103.
[7] 谢华玲,吕璐成,杨艳萍. 全球冠状病毒疫苗专利分析[J]. 中国生物工程杂志, 2020, 40(1-2): 57-64.
[8] 井汇源,段二珍,董望. 体外转录的自我复制型mRNA疫苗研究进展*[J]. 中国生物工程杂志, 2020, 40(12): 25-30.
[9] 廖小艳,陈丽丽. COVID-19疫苗研究现状*[J]. 中国生物工程杂志, 2020, 40(12): 8-17.
[10] 冯雪娇,侯海龙,喻琼,王俊姝. 我国宫颈癌疫苗市场分析及对策研究*[J]. 中国生物工程杂志, 2020, 40(11): 96-101.
[11] 高彦,杜晶晶,王斌,刘琦,申志强. 气相色谱法对狂犬病疫苗灭活工艺中β-丙内酯研究[J]. 中国生物工程杂志, 2019, 39(6): 25-31.
[12] 杨琳,傅哲彦,吕正兵,舒建洪. 免疫佐剂分类及作用机制[J]. 中国生物工程杂志, 2019, 39(5): 114-119.
[13] 许嘉越,李紫倩,张革. 登革病毒3'UTRΔ30系列疫苗的研究进展[J]. 中国生物工程杂志, 2019, 39(3): 97-104.
[14] 蒋析文,董子维,刘悦,朱小亚. 生物标记物与精准医疗研究进展[J]. 中国生物工程杂志, 2019, 39(2): 74-81.
[15] 孙思,邱喻兰,颜菊荣,杨静,吴光英,王玲,胥文春. 重组质粒pcDNA3-dnaJ/蛋白DnaJ异源免疫诱导Th1和Th17细胞免疫应答抵抗肺炎链球菌感染 *[J]. 中国生物工程杂志, 2019, 39(12): 9-17.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会