迟缓爱德华氏菌（Edwardsiella Tarda）LuxS/AI-2群体感应系统研究
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摘要
从患病牙鲆中分离出迟缓爱德华氏菌株TX1,经报告菌株检测发现TX1有AI-2活性。用梯度PCR和Genome walking的方法克隆了TX1 luxS基因,将luxS基因在大肠杆菌DH5α中表达,证明其具有功能活性。在TX1中,luxS的表达与AI-2的活性基本是一致的,二者均受生长时期和生长条件的调节,即在glucose存在的条件下luxS表达和AI-2活性升高,而在高温条件下luxS表达和AI-2活性降低。glucose对AI-2活性以及luxS表达的影响经过荧光定量PCR,启动子活性检测,AI-2活性检测以及凝胶滞缓等一系列的实验证实是由cAMP-CRP复合物介导的,该复合物可以通过与luxS启动子相互作用而抑制luxS的表达。RNA干扰表明,TX1中luxS表达被干扰以后,对细菌产生了多方面的影响,包括:(1)降低AI-2水平;(2)降低细菌的生长能力;(3)降低Ⅲ型分泌系统相关基因的表达水平以及生物膜的形成能力;(4)减弱细菌毒力。外源AI-2的添加可以回复Ⅲ型分泌系统相关基因的表达水平以及生物膜的形成,但是并不能修复生长状况,表明LuxS在TX1中具有双重功能,即参与细胞代谢以及群体感应信号传导。基于LuxS/AI-2群体感应系统对细菌毒力的重要性,设计并筛选了一个该系统的阻遏因子5411。Pull-down实验证明5411可以和LuxS特异性结合。研究表明5411在TX1中表达导致细菌毒力显著下降。将5411克隆至牙鲆共生菌FP3中,发现5411可以被分泌到胞外并能被TX1吸收。将表达5411的共生菌导入牙鲆,发现其能够有效阻遏TX1对牙鲆的侵染。
这些结果表明:(1) TX1中AI-2的活性受控于LuxS,而后者则受生长时期和生长条件的调控;(2) luxS的正常表达对于细菌的正常生长和侵染是必需的;(3) LuxS/AI-2群体感应系统调控Ⅲ型分泌系统相关毒力因子的表达;(4)通过阻遏LuxS/AI-2群体感应系统来抑制病原菌侵染是一种具有潜力的新型病害防控方法。
Edwardsiella tarda is a bacterial pathogen that can infect both humans and animals.TX1,an Ed.tarda strain isolated from diseased fish,was found to produce autoinducer 2(AI-2)-like activity that was growth phase dependent and modulated by growth conditions.The gene coding for the AI-2 synthase was cloned from TX1 and designated luxS.LuxS was able to complement the AI-2 mutant phenotype of Escherichia coli strain DH5α.Expression of luxS correlated with AI-2 activity and was increased by glucose and decreased by elevated temperature.The effect of glucose was shown to be mediated through the cAMP-CRP complex,which repressed luxS expression.Overexpression of luxS enhanced AI-2 activity in TX1,whereas disruption of luxS expression by antisense RNA interference(ⅰ) reduced the level of AI-2 activity,(ⅱ) impaired bacterial growth under various conditions,(ⅲ) weakened the expression of genes associated with the typeⅢsecretion system and biofilm formation,and(ⅳ) attenuated bacterial virulence.Addition of exogenous AI-2 was able to complement the deficiencies in the expression of TTSS genes and biofilm production but failed to rescue the growth defects.A small peptide 5411 was designed based on the sequence of luxS.5411 expressed by E.coli DH5αand the commensal strain FP3 could be secreted out of the cells and absorbed by E.tarda.Fish administered with FP3 expressing 5411 showed enhanced resistance against E.tarda infection.
Our results(ⅰ) demonstrated that the AI-2 activity in TX1 is controlled at least in part at the level of luxS expression,which in turn is regulated by growth conditions, and that the temporal expression of luxS is essential for optimal bacterial infection and survival;(ⅱ) suggested the existence in E.tarda of a LuxS/AI-2-mediated signal transduction pathway that regulates the production of virulence-associated elements. (ⅲ) suggested that LuxS inhibitory peptides might be used as an effective means to control bacterial infections.
这些结果表明:(1) TX1中AI-2的活性受控于LuxS,而后者则受生长时期和生长条件的调控;(2) luxS的正常表达对于细菌的正常生长和侵染是必需的;(3) LuxS/AI-2群体感应系统调控Ⅲ型分泌系统相关毒力因子的表达;(4)通过阻遏LuxS/AI-2群体感应系统来抑制病原菌侵染是一种具有潜力的新型病害防控方法。
Edwardsiella tarda is a bacterial pathogen that can infect both humans and animals.TX1,an Ed.tarda strain isolated from diseased fish,was found to produce autoinducer 2(AI-2)-like activity that was growth phase dependent and modulated by growth conditions.The gene coding for the AI-2 synthase was cloned from TX1 and designated luxS.LuxS was able to complement the AI-2 mutant phenotype of Escherichia coli strain DH5α.Expression of luxS correlated with AI-2 activity and was increased by glucose and decreased by elevated temperature.The effect of glucose was shown to be mediated through the cAMP-CRP complex,which repressed luxS expression.Overexpression of luxS enhanced AI-2 activity in TX1,whereas disruption of luxS expression by antisense RNA interference(ⅰ) reduced the level of AI-2 activity,(ⅱ) impaired bacterial growth under various conditions,(ⅲ) weakened the expression of genes associated with the typeⅢsecretion system and biofilm formation,and(ⅳ) attenuated bacterial virulence.Addition of exogenous AI-2 was able to complement the deficiencies in the expression of TTSS genes and biofilm production but failed to rescue the growth defects.A small peptide 5411 was designed based on the sequence of luxS.5411 expressed by E.coli DH5αand the commensal strain FP3 could be secreted out of the cells and absorbed by E.tarda.Fish administered with FP3 expressing 5411 showed enhanced resistance against E.tarda infection.
Our results(ⅰ) demonstrated that the AI-2 activity in TX1 is controlled at least in part at the level of luxS expression,which in turn is regulated by growth conditions, and that the temporal expression of luxS is essential for optimal bacterial infection and survival;(ⅱ) suggested the existence in E.tarda of a LuxS/AI-2-mediated signal transduction pathway that regulates the production of virulence-associated elements. (ⅲ) suggested that LuxS inhibitory peptides might be used as an effective means to control bacterial infections.
引文
1 H.On a new bacterium Paracolobactrum anguillimortiferumn.Bulletin of the Japanese Society of Scientific Fisheries,1962,28:162-164
Ewing W H,McWhorter A C,Eseobar M R,et al.Edwardsiella,a genus of Enterobacteriaceae based on a new species,E tarda.Int.Bul.Bact.Nomencl.Toxon.,1965,15:33-38
3 周常义,陈晓凤,何仲京.牛蛙迟缓爱德华氏菌变异株K的分离与鉴定.集美大学学报(自然科学版),2004,9(1):26-31
4 马勋,欧阳志明,陈怀清等.迟钝爱德华氏菌对HEp-2细胞的侵袭特性.微生物学报,1998,38(5):336-340
5 蔡完其,孙佩芳.中华鳖爱德华氏菌病病原和组织病理研究.水产学报,1997,21(4):428-433
6 Cook R A,Tappo J P.Chronic enteritis associated with Edwardsiella tarda infection in Rockhopper penguins.J Am Vet Med Assoc,1985,187(11):1219-1220
7 GrimontP A D.Edwardsiella hoshinae,a new species of Enterobacteriaceae.Curr.Mierobiol,1980,4:345-351
8 Wakabayashi H E S.Edwardsiella tarda(Paracolobaetrum anguillimortiferum)associated with pond-cultured eel disease.Bulletin of the Japanese Society of Scientific Fisheries,1973,39(9):931-936
9 Tamura K,Sakazaki R,McWhorter A C,et al.Edwardsiella tarda serotyping scheme for international use.J Clin Microbiol,1988,26(11):2343-2346
10 Watson J J,White F H.Hemolysins of Edwardsiella tarda.Can J Comp Med,1979,43(1):78-83
11 Chen J D,Huang S L.Hemolysin from Edwardsiella tarda strain ET16 isolated from eel Anguilla japonica identified as a hole-forming toxin.Fisheries Sci,1996,62(4):538-542
12 Hirono I,Tange N,Aoki T.Iron-regulated haemolysin gene from Edwardsiella tarda.Mol Microbiol,1997,24(4):851-856
13 Ullah A,Arai T.Pathological activities of the naturally occurring strains of Edwardsiella tarda isolated from diseased eels and flounders.Fish Pathol,1983,18(2):65-70
14 Suprapto H,Hara T,Nakai T,et al.Purification of a lethal toxin of Edwardsiella tarda.Fish Pathol,1996,31(4):203-207
15 Thanassi D G,Hultgren S J.Multiple pathways allow protein secretion across the bacterial outer membrane.Curr Opin Cell Biol,2000,12(4):420-430
16 Economou A,Christie P J,Fernandez R C,et al.Secretion by numbers:Protein traffic in prokaryotes.Mol Microbiol,2006,62(2):308-319
17 Yahr T L.A critical new pathway for toxin secretion? N Engl J Med,2006,355(11):1171-1172
18 Kubori T,Matsushima Y,Nakamura D,et al.Supramolecular structure of the Salmonella typhimurium type Ⅲ protein secretion system.Science,1998,280(5363):602-605
19 Zheng J,Leung K Y.Dissection of a type Ⅵ secretion system in Edwardsiella tarda.Mol Microbiol,2007,66(5):1192-1206
20 Tan Y P,Zheng J,Tung S L,et al.,Role of type Ⅲ secretion in Edwardsiella tarda virulence.2005,Soc General Microbiol.2301-2313.
21 薛淑霞,冯守明,孙金生.海水工厂化养殖大菱鲆(Scophthalmus maximus)和褐牙鲆(Paralichthys olivaceus)腹水病病原菌的分离与鉴定.海洋与湖沼,2006,37(6):548-554
22 Kawai K,Liu Y,Ohnishi K,et al.A conserved 37 kDa outer membrane protein of Edwardsiella tarda is an effective vaccine candidate.Vaccine,2004,22(25-26):3411-3418
23 张艳秋,詹勇,许梓荣.鱼类免疫机制及其影响因子.水产养殖,2005,26(003):1-5
24 黄新新,陆承平.迟缓爱德华菌全菌及外膜蛋白的免疫力比较.免疫学杂志,2002,18(003):187-189
25 Bassler B L,Wright M,Showalter R E,et al.Intercellular signalling in Vibrio harveyi:sequence and function of genes regulating expression of luminescence.Mol Microbiol,1993,9(4):773-786
26 Bassler B L,Wright M,Silverman M R.Multiple signalling systems controlling expression of luminescence in Vibrio harveyi:sequence and function of genes encoding a second sensory pathway.Mol Microbiol,1994,13(2):273-286
27 Nealson K H,Hastings J W.Bacterial bioluminescence:its control and ecological significance.Mierobiol Mol Biol R,1979,43(4):496-518
28 Nealson K H,Platt T,Hastings J W.Cellular Control of the Synthesis and Activity of the Bacterial Luminescent System.J Bacteriol,1970,104(1):313-322
29 Engebrecht J,Nealson K,Silverman M.Bacterial bioluminescenee:isolation and genetic analysis off-unctions from Vibrio fischeri.Cell,1983,32(3):773-781
30 Engebrecht J A,Silverman M.Identification of Genes and Gene Products Necessary for Bacterial Bioluminescence.P Natl Acad Sci USA,1984,81(13):4154-4158
31 Miyamoto C M,Boylan M,Graham A F,et al.Organization of the lux structural genes of Vibrio harveyi Expression under the T7 bacteriophage promoter,mRNA analysis,and nucleotide sequence of the luxD gene.J Biol Chem,1988,263(26):13393-13399
32 Waters C M,Bassler B L.Quorum sensing:cell-to-cell communication in bacteria.Annu Rev Cell Dev Bi,2005,21:319-346
33 Dong Y H,Xu J L,Li X Z,et al.AiiA,an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora.P Natl Acad Sci USA,2000,97(7):3526-3531
34 Bassler B L,Greenberg E P,Stevens A M.Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi.J Bacteriol,1997,179(12):4043-4045
35 Schauder S,Bassler B L.The languages of bacteria.Genes Dev,2001,15(12):1468-1480
36 Croxatto A,Chalker V J,Lauritz J,et al.VanT,a Homologue of Vibrio harveyi LuxR,Regulates Serine,Metalloprotease,Pigment,and Biofilm Production in Vibrio anguillarum.J Bacteriol,2002,184(6):1617-1629
37 Surette M G,Miller M B,Bassler B L.Quorum sensing in Escherichia coil,Salmonella typhimurium and Vibrio harveyi:A new family of genes responsible for autoinducer production.1999,P Natl Acad Sci USA.1639-1644.
38 Federle M J,Bassler B L.Interspecies communication in bacteria.J Clin Invest,2003,112(9):1291-1299
39 Miller M B,Bassler B L.Quorum sensing in bacteria.Annu Rev Microbiol,2001,55: 165-199
40 Beeston A L,Surette M G.pfs-dependent regulation of autoinducer 2 production in Salmonella enterica serovar Typhimurium.J Bacteriol,2002,184(13):3450-3456
41 Sperandio V,Torres A G,Jarvis B,et al.Bacteria-host communication:The language of hormones.P Natl Acad Sci USA,2003,100(15):8951-8956
42 Chen X I N,Schauder S,Potier N,et al.Structural identification of a bacterial quorum-sensing signal containing boron.Nature(London),2002,415(6871):545-549
43 Miller S T,Xavier K B,Campagna S R,et al.Salmonella typhimurium Recognizes a Chemically Distinct Form of the Bacterial Quorum-Sensing Signal AI-2.Mol Cell,2004,15(5):677,687
44 Sun J,Daniel R,Wagner D I,et al.Is autoinducer-2 a universal signal for interspecies communication:a comparative genomic and phylogenetic analysis of the synthesis and signal transduetion pathways.Brae Evol Biol,2004,4(36):1471-2148
45 Mok K C,Wingreen N S,Bassler B L.Vibrio harveyi quorum sensing:a coincidence detector for two autoinducers controls gene expression.EMBO J,2003,22:870-881
46 Mok K C,Wingreen N S,Bassler B L.Vibrio harveyi quorum sensing:a coincidence detector for two autoinducers controls gene expression.EMBO J,2003,22(4):870-881
47 Taga M E,Miller S T,Bassler B L.Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium.Mol Microbiol,2003,50(4):1411-1427
48 Taga M E,Semmelhack J L,Bassler B L.The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.Mol Microbiol,2001,42(3):777-793
49 Xavier K B,Bassler B L.Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli.J Bacteriol,2005,187(1):238-248
50 Hardie K R,Cooksley C,Green A D,et al.Autoinducer 2 activity in Escherichia coli culture supernatants can be actively reduced despite maintenance of an active synthase,LuxS.Microbiol,2003,149(3):715-728
51 Xavier K B,Bassler B L.Interference with AI-2-mediated bacterial cell-cell communication.Nature,2005,437(7059):750-753
52 Winzer K,Hardie K R,Williams P.Bacterial cell-to-cell communication:sorry,can't talk now-gone to lunch! Curr Opin Microbiol,2002,5(2):216-222
53 DeLisa M P,Valdes J J,Bentley W E.Mapping stress-induced changes in autoinducer AI-2 production in chemostat-cultivated Escherichia coli K-12.J Bacteriol,2001,183(9):2918-2928
54 Bassler B L,Wright M,Showalter R E,et al.Intercellular signalling in Vibrio harveyi:sequence and function of genes regulating expression of luminescence.Mol Microbiol,1993,9(4):773-786
55 Gonz(?)lez J E,Keshavan N D.Messing with Bacterial Quorum Sensing.Microbiol Mol Biol R,2006,70(4):859-875
56 McNab R,Ford S K,E1-Sabaeny A,et al.LuxS-Based Signaling in Streptococcus gordonii:Autoindueer 2 Controls Carbohydrate Metabolism and Biofilm Formation with Porphyrornonas gingivalis.J Baeteriol,2003,185(1):274-284
57 Rickard A H,Palmer R J,Blehert D S,et al.Autoinducer 2:a concentration-depondent signal for mutualistic bacterial biofilm growth.Mol Microbiol,2006,60(6):1446-1456
58 Surette M G,Bassler B L.Regulation of autoinducer production in Salmonella typhimurium.Mol Microbiol,1999,31(2):585-595
59 Xavier K B,Bassler B L.LuxS quorum sensing:more than just a numbers game.Curr Opin Microbiol,2003,6(2):191-197
60 Lyon W R,Madden J C,Levin J C,et al.Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes.Mol Microbiol,2001,42(1):145-157
61 Marouni M J,Sela S.The luxS gene of Streptococcus pyogenes regulates expression of genes that affect internalization by epithelial cells.Infect Immun,2003,71(10):5633-5639
62 Ohtani K,Hayashi H,Shimizu T.The luxS gone is involved in cell-cell signalling for toxin production in Clostridium perfringens.Mol Microbiol,2002,44(1):171-179
63 Stroeher U H,Paton A W,Ogunniyi A D,et al.Mutation of luxS of Streptococcus pneumoniae Affects Virulence in a Mouse Model Editor:AD O'Brien.Infect and Immun,2003,71(6):3206-3212
64 Winzer K,Sun Y,Green A,et al.,Role of Neisseria meningitidis luxS in Cell-to-Cell Signaling and Bacteremic Infection.Am Soc Microbiol,2002,2245-2248.
65 Zhu J,Miller M B,Vance R E,et al.Quorum-sensing regulators control virulence gene expression in Vibrio cholerae.P Natl Acad Sci USA,2002:3129-3134
66 DeLisa M P,Valdes J J,Bentley W E.Quorum signaling via AI-2 communicates the 'Metabolic Burden' associated with heterologous protein production in Escherichia coli.Biotechnol Bioeng,2001,75(4):439-450
67 Joyce E A,Kawale A,Censini S,et al.LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes.Infect Immun,2004,72(5):2964-2975
68 Merritt J,Kreth J,Shi W,et al.LuxS controls bacteriocin production in Streptococcus mutans through a novel regulatory component.Mol Microbiol,2005,57(4):960-969
69 Ren D,Bedzyk L A,Ye R W,et al.Differential gent expression shows natural brominated furanones interfere with the autoinducer-2 bacterial signaling system of Escherichia coil Biotechnol Bioeng,2004,88(5):630-642
70 Yuan L,Hillman J D,Progulske F A.Microarray Analysis of Quorum-Sensing-Regulated Genes in Porphyromonas gingivalis.Infect Immun,2005,73(7):4146-4154
71 Zhou L,Lei X H,Bochner B R,et al.Phenotype microarray analysis of Escherichia coli K-12 mutants with deletions of all two-component systems.J Bacteriol,2003,185(16):4956-4972
72 Henke J M,Bassler B L.Bacterial social engagements.Trends Cell Biol,2004,14(11):648-656
73 Williams S C,Patterson E K,Carry N L,et al.Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells.J Bacteriol,2004,186(8):2281-2287
74 Costerton J W,Stewart P S,Greenberg E P.Bacterial Biofilms:A Common Cause of Persistent Infections.Science,1999,284(5418):1318-1322
75 Stickler D J,Evans A,Morris N,et al.Strategies for the control of catheter encrustation.Int J Antimicrob Ag,2002,19(6):499-506
76 Ramos C,Licht T R,Sternberg C,et al.Monitoring bacterial growth activity in biofilms from laboratory flow chambers,plant rhizosphere,and animal intestine.Method Enzymol, 2001,337:21-42
77 Poschet J F,Boucher J C,Firoved A M,et al.Conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients.Method Enzymol,2001,336:65-76
78 McLeod B R,Fortun S,Costerton J W,et al.Enhanced bacterial biofilm control using electromagnetic fields in combination with antibiotics.Method Enzymol,1999,310:656-670
79 Hentzer M,Riedel K,Rasmussen T B,et al.Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound.Microbiology,2002,148(1):87-102
80 Defoirdt T,Boon N,Bossier P,et al.Disruption of bacterial quorum sensing:an unexplored strategy to fight infections in aquaculture.Aquaculture,2004,240(1-4):69-88
81 Lyon G J,Wright J S,Christopoulos A,et al.Reversible and specific extracellular antagonism of receptor-histidine kinase signaling.J Biol Chem,2002,277(8):6247-6253
82 Lin Y H,Xu J L,Hu J,et al.Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes.Mol Mierobiol,2003,47(3):849-860
83 Givskov M,De Nys R,Manefield M,et al.Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling.J Bacteriol,1996,178(22):6618-6622
84 Rothfork J M,Timmins G S,Harris M N,et al.Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants:new role for the NADPH oxidase in host defense.P Natl Acad Sci USA,2004,101(38):13867-13872
85 郭嘉亮,陈卫民.细菌群体感应信号分子与抑制剂研究进展.生命科学,2007,19(2):224-232
86 Morohoshi T,Inaba T,Kato N,et al.Identification of quorum-sensing signal molecules and the LuxRI homologs in fish pathogen Edwardsiella tarda.J Biosci Bioeng,2004,98(4):274-281
87 Surette M G,Bassler B L.Quorum sensing in Escherichia coli and Salmonella typhimurium.Proc Natl Acad Sci USA,1998,95(12):7046-7050
88 G-reenberg E P,Hastings J W,Ulitzur S.Induction of luciferase synthesis in Beneckea harveyi by other marine bacteria.Arch Microbiol,1979,120(2):87-91
89 Syn C K C,Swarup S.A scalable protocol for the isolation of large-sized genomic DNA within an hour from several bacteria.Anal Biochem,2000,278(1):86-90
90 Das S K,Sedelnikova S E,Baker P J,et al.Cloning,purification,crystallization and preliminary crystallographic analysis of Bacillus subtilis LuxS.Acta Crystallogr D Biol Crystallogr,2001,57(9):1324-1325
91 Hilgers M T,Ludwig M L.Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site.Proc Natl Acad Sci,2001,98(20):11169-11174
92 Lewis H A,Furlong E B,Laubert B,et al.A structural genomics approach to the study of quorum sensing:crystal structures of three LuxS orthologs.Structure,2001,9(6):527-537
93 Ruzheinikov S N,Das S K,Sedelnikova S E,et al.The 1.2 A structure of a novel quorum-sensing protein,Bacillus subtilis LuxS.J Mol Biol,2001,313(1):111-122
94 Rajah R,Zhu J,Hu X,et al.Crystal structure of S-dbosylhomocysteinase(LuxS) in complex with a catalytic 2-ketone intermediate.Biochemistry,2005,44(10):3745-3753
95 De Keersmaecker S C,Sonck K,Vanderleyden J.Let LuxS speak up in AI-2 signaling.Trends Microbiol,2006,14(3):114-119
96 Zhu J,Dizin E,Hu X,et al.S-Ribosylhomocysteinase(LuxS) is a mononuclear iron protein.Biochemistry,2003,42(16):4717-4726
97 Gattiker A,Gasteiger E,Bairoch A.ScanProsite:a reference implementation of a PROSITE scanning tool.Appl Bioinformatics,2002,1(2):107-108
98 Cozzone A J.Protein phosphorylation on tyrosine in bacteria.Arch.Microbiology,2004,181:171-181
99 Vincent C,Duclos B,Grangeasse C,et al.Relationship between exopolysaccharide production and protein-tyrosine phosphorylation in gram-negative bacteria.J MolBiol,2000,304(3):311-321
100 De Keersmaecker S C J,Varszegi C,van Boxel N,et al.Chemical synthesis of(S)-4,5-dihydroxy-2,3-pentanedione,a bacterial signal molecule precursor,and validation of its activity in Salmonella typhimurium.J Biol Chem,2005,280(20):19563
101 Prouty A M,Schwesinger W H,Gunn J S.Biofilm Formation and Interaction with the Surfaces of Gallstones by Salmonella spp.Editor:BB Finlay.Infect Immun,2002,70(5):2640-2649
102 Doherty N,Holden M T G,Qazi S N,et al.Functional analysis of luxS in Staphylococcus aureus reveals a role in metabolism but not quorum sensing.J Bacteriol,2006,188(8):2885-2897
103 Wang L,Hashimoto Y,Tsao C Y,et al.Cyclic AMP(cAMP) and cAMP receptor protein influence both synthesis and uptake of extracellular autoinducer 2 in Escherichia coli.J Bacteriol,2005,187(6):2066-2076
104 Han X G,Lu C P.Detection of Autoinducer-2 and Analysis of the Profile of luxS and pfs Transcription in Streptococcus suis Serotype 2.Curr Microbiol,2009,58(2):146-152
105 Bruckner R T,itgemeyer F.Carbon catabolite repression in bacteria:choice of the carbon source and autoregulatory limitation of sugar utilization.FEMS Microbiol Lett,2002,209(2):141-148
106 Kolb A,Busby S,Buc Ⅱ,et al.Transcriptional regulation by cAMP and its receptor protein.Annu Rev Biochem,1993,62(1):749-797
107 St(u|¨)lke J,Hillen W.Carbon catabolite repression in bacteria.Curr Opin Microbiol,1999,2(2):195-201
108 Deutscher J,Francke C,Postma P W.How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria? Microbiol Biol R,2006,70(4):939-1031
109 Marx C J,Lidstrom M E.Development of improved versatile broad-host-range vectors for use in methylotrophs and other Gram-negative bacteria.Microbiology,2001,147(8):2065-2075
110 Livak K J,Schmittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2~(-ΔΔct) Method.Methods,2001,25(4):402-408
111 Sun L,Dove S L,Panaghie G,et al.An RNA polymerase mutant deficient in DNA melting facilitates study of activation mechanism:application to an artificial activator of transcription.J Mol Biol,2004,343(5):1171-1182
112 Taga M E,Semmelhack J L,Bassler B L.The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.Mol Microbiol,2001,42(3):777-793
113 Asanuma N,Yoshii T,Hino T.Molecular characterization and transcription of the luxS gene that encodes LuxS autoinducer 2 synthase in Streptococcus bovis.Curr Microbiol,2004,49(5):366-371
114 Xu L,Li H,Vuong C,et al.Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis.Infect Immun,2006,74(1):488-496
115 Vendeville A,Winzer K,Heurlier K,et al.Making'sense'of metabolism:autoinducer-2,LuxS and pathogenic bacteria.Nat Rev Microbiol,2005,3(5):383-396
116 Winzer K,Hardie K R,Burgess N,et al.LuxS:its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.Microbiology,2002,148(4):909-922
117 Kendall M M,Rasko D A,Sperandio V.Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2,Autoinducer-3,and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli.Infect Immun,2007,75(10):4875-4884
118 Coulthurst S J,Clare S,Evans T J,et al.Quorum sensing has an unexpected role in virulence in the model pathogen Citrobacter rodentium.EMBO Rep,2007,8(7):698-703
119 Coulthurst S J,Kurz C L,Salmond G P C,luxS mutants of Serratia defective in autoinducer-2-dependent'quorum sensing'show strain-dependent impacts on virulence and production of carbapenem and prodigiosin.2004,Soc General Microbiol.901-1910.
120 Joyce E A,Kawale A,Censini S,et al.LuxS Is Required for Persistent Pneumococcal Carriage and Expression of Virulence and Biosynthesis Genes.Infect Immun,2004,72(5):2964-2975
121 Henke J M,Bassler B L.Bacterial social engagements.Trends cell Biol,2004,14(11):648-656
122 Henke J M,Bassler B L.Quorum sensing regulates type Ⅲ secretion in Vibrio harveyi and Vibrio parahaemolyticus.J Bacteriol,2004,186(12):3794-3805
123 Li J,Attila C,Wang L,et al.Quorum Sensing in Escherichia coli Is Signaled by AI-2/LsrR:Effects on Small RNA and Biofilm Architecture.J Bacteriol,2007,189(16):6011-6020
124 Sircili M P,Waiters M,Trabulsi L R,et al.Modulation of Enteropathogenic Escherichia coli Virulence by Quorum Sensing.Infect Immun,2004,72(4):2329-2337
125 Herzberg M,Kaye I K,Peti W,et al.YdgG(TqsA) controls biofilm formation in Escherichia coli K-12 through autoinducer 2 transport.J Bactefiol,2006,188(2):587-598
126 Li Y H,Tang N,Aspiras M B,et al.A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation.J Bacteriol,2002,184(10):2699-2708
127 McNab R,Ford S K,El-Sabaeny A,et al.LuxS-based signaling in Streptococcus gordonii:autoinducer 2 controls carbohydrate metabolism and biofilm formation with Porphyromonas gingivalis.J Baeteriol,2003,185(1):274-284
128 Rickard A H,Palmer R J,Blehert D S,et al.Autoinducer 2:a concentration-dependent signal for mutualistic bacterial biofilm growth.Mol Microbiol,2006,60(6):1446-1456
129 Winzer K,Sun Y H,Green A,et al.Role of Neisseria meningitidis luxS in cell-to-cell signaling and bacteremic infection.Infect Immun,2002,70(4):2245-2248
130 Kozlova E V,Popov V L,Sha J,et al.Mutation in the S-ribosylhomocysteinase(luxS)gene involved in quorum sensing affects biofilm formation and virulence in a clinical isolate of Aeromonas hydrophila.Microb Pathog,2008,45(5-6):343-354
131 Lyon W R,Madden J C,Levin J C,et al.Mutation of lugs affects growth and virulence factor expression in Streptococcus pyogenes.Mol Microbiol,2001,42(1):145-157
132 Stroeher U H,Paton A W,Ogunniyi A D,et al.Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model.Infect hnmun,2003,71(6):3206-3212
133 Sztajer H,Lemme A,Vilchez R,et al.Autoinducer-2-regulated genes in Streptococcus mutans UA 159 and global metabolic effect of the luxS mutation.J Bacteriol,2008,190(1):401-415
134 Osaki T,Hanawa T,Manzoku T,et al.Mutation of luxS affects motility and infectivity of Helicobacter pylori in gastric mucosa of a Mongolian gerbil model.J Med Microbiol,2006,55(11):1477-1485
135 Sela S,Frank S,Belausov E,et al.A Mutation in the luxS gene influences Listeria monocytogenes biofilm formation.Appl Environ Microbiol,2006,72(8):5653-5658
136 Merritt J,Qi F,Goodman S D,et al.Mutation of luxS affects biofilm formation in Streptococcus mutans.Infect Immun,2003,71(4):1972-1979
137 Schneider R,Lockatell C V,Johnson D,et al.Detection and mutation of a luxS-encoded autoinducer in Proteus mirabilis.Microbiology,2002,148(3):773-782
138 Manefield M,Rasmussen T B,Henzter M,et al.Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover.Microbiology,2002,148(4):1119-1127
139 Hentzer M,Wu H,Andersen J B,et al.Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors.EMBO J,2003,22(15):3803-3815
140 Wu H,Song Z,Hentzer M,et al.Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice.J Antimicrob Chemoth,2004,53(6):1054-1061
141 Ishida T,Ikeda T,Takiguchi N,et al.Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopcntylamides.Appl Environ Microbiol,2007,73(10):3183-3188
142 Hoffmann N,Lee B,Hentzer M,et al.Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudornonas aeruginosa and attenuates chronic P.aeruginosa lung infection in mice.Antimicrob Agents Ch,2007,51(10):3677-3687
143 Zheng F R,Sun X Q,Liu H Z,et al.Study on the distribution and expression of a DNA vaccine against lymphocystis disease virus in Japanese flounder(Paralichthys olivaceus).Aquaculture,2006,261(4):1128-1134
144 Manefield M,Rasmussen T B,Henzter M,et al.Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover.Microbiology,2002,148(4):1119-1127
145 Rasmussen T B,Sldndersoe M E,Bjarnsholt T,et al,Identity and effects of quorum-sensing inhibitors produced by Penicillium species.2005,Soc General Microbiol.1325-1340.
146 Bjarnsholt T,Jensen P O,Rasmussen T B,et al.,Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.2005,Soc General Microbiol.3873-3880.
147 Hoffmann N,Lee B,Hentzer M,et al.Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Psendomonas aeruginosa and attenuates chronic P.aeruginosa lung infection in Cftr(-/-) mice.Antimicrob Agents Chemoth,2007,51(10):3677-3687
148 Rasmussen T B,Bjarnsholt T,Skindersoe M E,et al.Screening for quorum-sensing inhibitors(QSI) by use of a novel genetic system,the QSI selector.J Bacteriol,2005,187(5):1799-1814
Ewing W H,McWhorter A C,Eseobar M R,et al.Edwardsiella,a genus of Enterobacteriaceae based on a new species,E tarda.Int.Bul.Bact.Nomencl.Toxon.,1965,15:33-38
3 周常义,陈晓凤,何仲京.牛蛙迟缓爱德华氏菌变异株K的分离与鉴定.集美大学学报(自然科学版),2004,9(1):26-31
4 马勋,欧阳志明,陈怀清等.迟钝爱德华氏菌对HEp-2细胞的侵袭特性.微生物学报,1998,38(5):336-340
5 蔡完其,孙佩芳.中华鳖爱德华氏菌病病原和组织病理研究.水产学报,1997,21(4):428-433
6 Cook R A,Tappo J P.Chronic enteritis associated with Edwardsiella tarda infection in Rockhopper penguins.J Am Vet Med Assoc,1985,187(11):1219-1220
7 GrimontP A D.Edwardsiella hoshinae,a new species of Enterobacteriaceae.Curr.Mierobiol,1980,4:345-351
8 Wakabayashi H E S.Edwardsiella tarda(Paracolobaetrum anguillimortiferum)associated with pond-cultured eel disease.Bulletin of the Japanese Society of Scientific Fisheries,1973,39(9):931-936
9 Tamura K,Sakazaki R,McWhorter A C,et al.Edwardsiella tarda serotyping scheme for international use.J Clin Microbiol,1988,26(11):2343-2346
10 Watson J J,White F H.Hemolysins of Edwardsiella tarda.Can J Comp Med,1979,43(1):78-83
11 Chen J D,Huang S L.Hemolysin from Edwardsiella tarda strain ET16 isolated from eel Anguilla japonica identified as a hole-forming toxin.Fisheries Sci,1996,62(4):538-542
12 Hirono I,Tange N,Aoki T.Iron-regulated haemolysin gene from Edwardsiella tarda.Mol Microbiol,1997,24(4):851-856
13 Ullah A,Arai T.Pathological activities of the naturally occurring strains of Edwardsiella tarda isolated from diseased eels and flounders.Fish Pathol,1983,18(2):65-70
14 Suprapto H,Hara T,Nakai T,et al.Purification of a lethal toxin of Edwardsiella tarda.Fish Pathol,1996,31(4):203-207
15 Thanassi D G,Hultgren S J.Multiple pathways allow protein secretion across the bacterial outer membrane.Curr Opin Cell Biol,2000,12(4):420-430
16 Economou A,Christie P J,Fernandez R C,et al.Secretion by numbers:Protein traffic in prokaryotes.Mol Microbiol,2006,62(2):308-319
17 Yahr T L.A critical new pathway for toxin secretion? N Engl J Med,2006,355(11):1171-1172
18 Kubori T,Matsushima Y,Nakamura D,et al.Supramolecular structure of the Salmonella typhimurium type Ⅲ protein secretion system.Science,1998,280(5363):602-605
19 Zheng J,Leung K Y.Dissection of a type Ⅵ secretion system in Edwardsiella tarda.Mol Microbiol,2007,66(5):1192-1206
20 Tan Y P,Zheng J,Tung S L,et al.,Role of type Ⅲ secretion in Edwardsiella tarda virulence.2005,Soc General Microbiol.2301-2313.
21 薛淑霞,冯守明,孙金生.海水工厂化养殖大菱鲆(Scophthalmus maximus)和褐牙鲆(Paralichthys olivaceus)腹水病病原菌的分离与鉴定.海洋与湖沼,2006,37(6):548-554
22 Kawai K,Liu Y,Ohnishi K,et al.A conserved 37 kDa outer membrane protein of Edwardsiella tarda is an effective vaccine candidate.Vaccine,2004,22(25-26):3411-3418
23 张艳秋,詹勇,许梓荣.鱼类免疫机制及其影响因子.水产养殖,2005,26(003):1-5
24 黄新新,陆承平.迟缓爱德华菌全菌及外膜蛋白的免疫力比较.免疫学杂志,2002,18(003):187-189
25 Bassler B L,Wright M,Showalter R E,et al.Intercellular signalling in Vibrio harveyi:sequence and function of genes regulating expression of luminescence.Mol Microbiol,1993,9(4):773-786
26 Bassler B L,Wright M,Silverman M R.Multiple signalling systems controlling expression of luminescence in Vibrio harveyi:sequence and function of genes encoding a second sensory pathway.Mol Microbiol,1994,13(2):273-286
27 Nealson K H,Hastings J W.Bacterial bioluminescence:its control and ecological significance.Mierobiol Mol Biol R,1979,43(4):496-518
28 Nealson K H,Platt T,Hastings J W.Cellular Control of the Synthesis and Activity of the Bacterial Luminescent System.J Bacteriol,1970,104(1):313-322
29 Engebrecht J,Nealson K,Silverman M.Bacterial bioluminescenee:isolation and genetic analysis off-unctions from Vibrio fischeri.Cell,1983,32(3):773-781
30 Engebrecht J A,Silverman M.Identification of Genes and Gene Products Necessary for Bacterial Bioluminescence.P Natl Acad Sci USA,1984,81(13):4154-4158
31 Miyamoto C M,Boylan M,Graham A F,et al.Organization of the lux structural genes of Vibrio harveyi Expression under the T7 bacteriophage promoter,mRNA analysis,and nucleotide sequence of the luxD gene.J Biol Chem,1988,263(26):13393-13399
32 Waters C M,Bassler B L.Quorum sensing:cell-to-cell communication in bacteria.Annu Rev Cell Dev Bi,2005,21:319-346
33 Dong Y H,Xu J L,Li X Z,et al.AiiA,an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora.P Natl Acad Sci USA,2000,97(7):3526-3531
34 Bassler B L,Greenberg E P,Stevens A M.Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi.J Bacteriol,1997,179(12):4043-4045
35 Schauder S,Bassler B L.The languages of bacteria.Genes Dev,2001,15(12):1468-1480
36 Croxatto A,Chalker V J,Lauritz J,et al.VanT,a Homologue of Vibrio harveyi LuxR,Regulates Serine,Metalloprotease,Pigment,and Biofilm Production in Vibrio anguillarum.J Bacteriol,2002,184(6):1617-1629
37 Surette M G,Miller M B,Bassler B L.Quorum sensing in Escherichia coil,Salmonella typhimurium and Vibrio harveyi:A new family of genes responsible for autoinducer production.1999,P Natl Acad Sci USA.1639-1644.
38 Federle M J,Bassler B L.Interspecies communication in bacteria.J Clin Invest,2003,112(9):1291-1299
39 Miller M B,Bassler B L.Quorum sensing in bacteria.Annu Rev Microbiol,2001,55: 165-199
40 Beeston A L,Surette M G.pfs-dependent regulation of autoinducer 2 production in Salmonella enterica serovar Typhimurium.J Bacteriol,2002,184(13):3450-3456
41 Sperandio V,Torres A G,Jarvis B,et al.Bacteria-host communication:The language of hormones.P Natl Acad Sci USA,2003,100(15):8951-8956
42 Chen X I N,Schauder S,Potier N,et al.Structural identification of a bacterial quorum-sensing signal containing boron.Nature(London),2002,415(6871):545-549
43 Miller S T,Xavier K B,Campagna S R,et al.Salmonella typhimurium Recognizes a Chemically Distinct Form of the Bacterial Quorum-Sensing Signal AI-2.Mol Cell,2004,15(5):677,687
44 Sun J,Daniel R,Wagner D I,et al.Is autoinducer-2 a universal signal for interspecies communication:a comparative genomic and phylogenetic analysis of the synthesis and signal transduetion pathways.Brae Evol Biol,2004,4(36):1471-2148
45 Mok K C,Wingreen N S,Bassler B L.Vibrio harveyi quorum sensing:a coincidence detector for two autoinducers controls gene expression.EMBO J,2003,22:870-881
46 Mok K C,Wingreen N S,Bassler B L.Vibrio harveyi quorum sensing:a coincidence detector for two autoinducers controls gene expression.EMBO J,2003,22(4):870-881
47 Taga M E,Miller S T,Bassler B L.Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium.Mol Microbiol,2003,50(4):1411-1427
48 Taga M E,Semmelhack J L,Bassler B L.The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.Mol Microbiol,2001,42(3):777-793
49 Xavier K B,Bassler B L.Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli.J Bacteriol,2005,187(1):238-248
50 Hardie K R,Cooksley C,Green A D,et al.Autoinducer 2 activity in Escherichia coli culture supernatants can be actively reduced despite maintenance of an active synthase,LuxS.Microbiol,2003,149(3):715-728
51 Xavier K B,Bassler B L.Interference with AI-2-mediated bacterial cell-cell communication.Nature,2005,437(7059):750-753
52 Winzer K,Hardie K R,Williams P.Bacterial cell-to-cell communication:sorry,can't talk now-gone to lunch! Curr Opin Microbiol,2002,5(2):216-222
53 DeLisa M P,Valdes J J,Bentley W E.Mapping stress-induced changes in autoinducer AI-2 production in chemostat-cultivated Escherichia coli K-12.J Bacteriol,2001,183(9):2918-2928
54 Bassler B L,Wright M,Showalter R E,et al.Intercellular signalling in Vibrio harveyi:sequence and function of genes regulating expression of luminescence.Mol Microbiol,1993,9(4):773-786
55 Gonz(?)lez J E,Keshavan N D.Messing with Bacterial Quorum Sensing.Microbiol Mol Biol R,2006,70(4):859-875
56 McNab R,Ford S K,E1-Sabaeny A,et al.LuxS-Based Signaling in Streptococcus gordonii:Autoindueer 2 Controls Carbohydrate Metabolism and Biofilm Formation with Porphyrornonas gingivalis.J Baeteriol,2003,185(1):274-284
57 Rickard A H,Palmer R J,Blehert D S,et al.Autoinducer 2:a concentration-depondent signal for mutualistic bacterial biofilm growth.Mol Microbiol,2006,60(6):1446-1456
58 Surette M G,Bassler B L.Regulation of autoinducer production in Salmonella typhimurium.Mol Microbiol,1999,31(2):585-595
59 Xavier K B,Bassler B L.LuxS quorum sensing:more than just a numbers game.Curr Opin Microbiol,2003,6(2):191-197
60 Lyon W R,Madden J C,Levin J C,et al.Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes.Mol Microbiol,2001,42(1):145-157
61 Marouni M J,Sela S.The luxS gene of Streptococcus pyogenes regulates expression of genes that affect internalization by epithelial cells.Infect Immun,2003,71(10):5633-5639
62 Ohtani K,Hayashi H,Shimizu T.The luxS gone is involved in cell-cell signalling for toxin production in Clostridium perfringens.Mol Microbiol,2002,44(1):171-179
63 Stroeher U H,Paton A W,Ogunniyi A D,et al.Mutation of luxS of Streptococcus pneumoniae Affects Virulence in a Mouse Model Editor:AD O'Brien.Infect and Immun,2003,71(6):3206-3212
64 Winzer K,Sun Y,Green A,et al.,Role of Neisseria meningitidis luxS in Cell-to-Cell Signaling and Bacteremic Infection.Am Soc Microbiol,2002,2245-2248.
65 Zhu J,Miller M B,Vance R E,et al.Quorum-sensing regulators control virulence gene expression in Vibrio cholerae.P Natl Acad Sci USA,2002:3129-3134
66 DeLisa M P,Valdes J J,Bentley W E.Quorum signaling via AI-2 communicates the 'Metabolic Burden' associated with heterologous protein production in Escherichia coli.Biotechnol Bioeng,2001,75(4):439-450
67 Joyce E A,Kawale A,Censini S,et al.LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes.Infect Immun,2004,72(5):2964-2975
68 Merritt J,Kreth J,Shi W,et al.LuxS controls bacteriocin production in Streptococcus mutans through a novel regulatory component.Mol Microbiol,2005,57(4):960-969
69 Ren D,Bedzyk L A,Ye R W,et al.Differential gent expression shows natural brominated furanones interfere with the autoinducer-2 bacterial signaling system of Escherichia coil Biotechnol Bioeng,2004,88(5):630-642
70 Yuan L,Hillman J D,Progulske F A.Microarray Analysis of Quorum-Sensing-Regulated Genes in Porphyromonas gingivalis.Infect Immun,2005,73(7):4146-4154
71 Zhou L,Lei X H,Bochner B R,et al.Phenotype microarray analysis of Escherichia coli K-12 mutants with deletions of all two-component systems.J Bacteriol,2003,185(16):4956-4972
72 Henke J M,Bassler B L.Bacterial social engagements.Trends Cell Biol,2004,14(11):648-656
73 Williams S C,Patterson E K,Carry N L,et al.Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells.J Bacteriol,2004,186(8):2281-2287
74 Costerton J W,Stewart P S,Greenberg E P.Bacterial Biofilms:A Common Cause of Persistent Infections.Science,1999,284(5418):1318-1322
75 Stickler D J,Evans A,Morris N,et al.Strategies for the control of catheter encrustation.Int J Antimicrob Ag,2002,19(6):499-506
76 Ramos C,Licht T R,Sternberg C,et al.Monitoring bacterial growth activity in biofilms from laboratory flow chambers,plant rhizosphere,and animal intestine.Method Enzymol, 2001,337:21-42
77 Poschet J F,Boucher J C,Firoved A M,et al.Conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients.Method Enzymol,2001,336:65-76
78 McLeod B R,Fortun S,Costerton J W,et al.Enhanced bacterial biofilm control using electromagnetic fields in combination with antibiotics.Method Enzymol,1999,310:656-670
79 Hentzer M,Riedel K,Rasmussen T B,et al.Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound.Microbiology,2002,148(1):87-102
80 Defoirdt T,Boon N,Bossier P,et al.Disruption of bacterial quorum sensing:an unexplored strategy to fight infections in aquaculture.Aquaculture,2004,240(1-4):69-88
81 Lyon G J,Wright J S,Christopoulos A,et al.Reversible and specific extracellular antagonism of receptor-histidine kinase signaling.J Biol Chem,2002,277(8):6247-6253
82 Lin Y H,Xu J L,Hu J,et al.Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes.Mol Mierobiol,2003,47(3):849-860
83 Givskov M,De Nys R,Manefield M,et al.Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling.J Bacteriol,1996,178(22):6618-6622
84 Rothfork J M,Timmins G S,Harris M N,et al.Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants:new role for the NADPH oxidase in host defense.P Natl Acad Sci USA,2004,101(38):13867-13872
85 郭嘉亮,陈卫民.细菌群体感应信号分子与抑制剂研究进展.生命科学,2007,19(2):224-232
86 Morohoshi T,Inaba T,Kato N,et al.Identification of quorum-sensing signal molecules and the LuxRI homologs in fish pathogen Edwardsiella tarda.J Biosci Bioeng,2004,98(4):274-281
87 Surette M G,Bassler B L.Quorum sensing in Escherichia coli and Salmonella typhimurium.Proc Natl Acad Sci USA,1998,95(12):7046-7050
88 G-reenberg E P,Hastings J W,Ulitzur S.Induction of luciferase synthesis in Beneckea harveyi by other marine bacteria.Arch Microbiol,1979,120(2):87-91
89 Syn C K C,Swarup S.A scalable protocol for the isolation of large-sized genomic DNA within an hour from several bacteria.Anal Biochem,2000,278(1):86-90
90 Das S K,Sedelnikova S E,Baker P J,et al.Cloning,purification,crystallization and preliminary crystallographic analysis of Bacillus subtilis LuxS.Acta Crystallogr D Biol Crystallogr,2001,57(9):1324-1325
91 Hilgers M T,Ludwig M L.Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site.Proc Natl Acad Sci,2001,98(20):11169-11174
92 Lewis H A,Furlong E B,Laubert B,et al.A structural genomics approach to the study of quorum sensing:crystal structures of three LuxS orthologs.Structure,2001,9(6):527-537
93 Ruzheinikov S N,Das S K,Sedelnikova S E,et al.The 1.2 A structure of a novel quorum-sensing protein,Bacillus subtilis LuxS.J Mol Biol,2001,313(1):111-122
94 Rajah R,Zhu J,Hu X,et al.Crystal structure of S-dbosylhomocysteinase(LuxS) in complex with a catalytic 2-ketone intermediate.Biochemistry,2005,44(10):3745-3753
95 De Keersmaecker S C,Sonck K,Vanderleyden J.Let LuxS speak up in AI-2 signaling.Trends Microbiol,2006,14(3):114-119
96 Zhu J,Dizin E,Hu X,et al.S-Ribosylhomocysteinase(LuxS) is a mononuclear iron protein.Biochemistry,2003,42(16):4717-4726
97 Gattiker A,Gasteiger E,Bairoch A.ScanProsite:a reference implementation of a PROSITE scanning tool.Appl Bioinformatics,2002,1(2):107-108
98 Cozzone A J.Protein phosphorylation on tyrosine in bacteria.Arch.Microbiology,2004,181:171-181
99 Vincent C,Duclos B,Grangeasse C,et al.Relationship between exopolysaccharide production and protein-tyrosine phosphorylation in gram-negative bacteria.J MolBiol,2000,304(3):311-321
100 De Keersmaecker S C J,Varszegi C,van Boxel N,et al.Chemical synthesis of(S)-4,5-dihydroxy-2,3-pentanedione,a bacterial signal molecule precursor,and validation of its activity in Salmonella typhimurium.J Biol Chem,2005,280(20):19563
101 Prouty A M,Schwesinger W H,Gunn J S.Biofilm Formation and Interaction with the Surfaces of Gallstones by Salmonella spp.Editor:BB Finlay.Infect Immun,2002,70(5):2640-2649
102 Doherty N,Holden M T G,Qazi S N,et al.Functional analysis of luxS in Staphylococcus aureus reveals a role in metabolism but not quorum sensing.J Bacteriol,2006,188(8):2885-2897
103 Wang L,Hashimoto Y,Tsao C Y,et al.Cyclic AMP(cAMP) and cAMP receptor protein influence both synthesis and uptake of extracellular autoinducer 2 in Escherichia coli.J Bacteriol,2005,187(6):2066-2076
104 Han X G,Lu C P.Detection of Autoinducer-2 and Analysis of the Profile of luxS and pfs Transcription in Streptococcus suis Serotype 2.Curr Microbiol,2009,58(2):146-152
105 Bruckner R T,itgemeyer F.Carbon catabolite repression in bacteria:choice of the carbon source and autoregulatory limitation of sugar utilization.FEMS Microbiol Lett,2002,209(2):141-148
106 Kolb A,Busby S,Buc Ⅱ,et al.Transcriptional regulation by cAMP and its receptor protein.Annu Rev Biochem,1993,62(1):749-797
107 St(u|¨)lke J,Hillen W.Carbon catabolite repression in bacteria.Curr Opin Microbiol,1999,2(2):195-201
108 Deutscher J,Francke C,Postma P W.How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria? Microbiol Biol R,2006,70(4):939-1031
109 Marx C J,Lidstrom M E.Development of improved versatile broad-host-range vectors for use in methylotrophs and other Gram-negative bacteria.Microbiology,2001,147(8):2065-2075
110 Livak K J,Schmittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2~(-ΔΔct) Method.Methods,2001,25(4):402-408
111 Sun L,Dove S L,Panaghie G,et al.An RNA polymerase mutant deficient in DNA melting facilitates study of activation mechanism:application to an artificial activator of transcription.J Mol Biol,2004,343(5):1171-1182
112 Taga M E,Semmelhack J L,Bassler B L.The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.Mol Microbiol,2001,42(3):777-793
113 Asanuma N,Yoshii T,Hino T.Molecular characterization and transcription of the luxS gene that encodes LuxS autoinducer 2 synthase in Streptococcus bovis.Curr Microbiol,2004,49(5):366-371
114 Xu L,Li H,Vuong C,et al.Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis.Infect Immun,2006,74(1):488-496
115 Vendeville A,Winzer K,Heurlier K,et al.Making'sense'of metabolism:autoinducer-2,LuxS and pathogenic bacteria.Nat Rev Microbiol,2005,3(5):383-396
116 Winzer K,Hardie K R,Burgess N,et al.LuxS:its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.Microbiology,2002,148(4):909-922
117 Kendall M M,Rasko D A,Sperandio V.Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2,Autoinducer-3,and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli.Infect Immun,2007,75(10):4875-4884
118 Coulthurst S J,Clare S,Evans T J,et al.Quorum sensing has an unexpected role in virulence in the model pathogen Citrobacter rodentium.EMBO Rep,2007,8(7):698-703
119 Coulthurst S J,Kurz C L,Salmond G P C,luxS mutants of Serratia defective in autoinducer-2-dependent'quorum sensing'show strain-dependent impacts on virulence and production of carbapenem and prodigiosin.2004,Soc General Microbiol.901-1910.
120 Joyce E A,Kawale A,Censini S,et al.LuxS Is Required for Persistent Pneumococcal Carriage and Expression of Virulence and Biosynthesis Genes.Infect Immun,2004,72(5):2964-2975
121 Henke J M,Bassler B L.Bacterial social engagements.Trends cell Biol,2004,14(11):648-656
122 Henke J M,Bassler B L.Quorum sensing regulates type Ⅲ secretion in Vibrio harveyi and Vibrio parahaemolyticus.J Bacteriol,2004,186(12):3794-3805
123 Li J,Attila C,Wang L,et al.Quorum Sensing in Escherichia coli Is Signaled by AI-2/LsrR:Effects on Small RNA and Biofilm Architecture.J Bacteriol,2007,189(16):6011-6020
124 Sircili M P,Waiters M,Trabulsi L R,et al.Modulation of Enteropathogenic Escherichia coli Virulence by Quorum Sensing.Infect Immun,2004,72(4):2329-2337
125 Herzberg M,Kaye I K,Peti W,et al.YdgG(TqsA) controls biofilm formation in Escherichia coli K-12 through autoinducer 2 transport.J Bactefiol,2006,188(2):587-598
126 Li Y H,Tang N,Aspiras M B,et al.A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation.J Bacteriol,2002,184(10):2699-2708
127 McNab R,Ford S K,El-Sabaeny A,et al.LuxS-based signaling in Streptococcus gordonii:autoinducer 2 controls carbohydrate metabolism and biofilm formation with Porphyromonas gingivalis.J Baeteriol,2003,185(1):274-284
128 Rickard A H,Palmer R J,Blehert D S,et al.Autoinducer 2:a concentration-dependent signal for mutualistic bacterial biofilm growth.Mol Microbiol,2006,60(6):1446-1456
129 Winzer K,Sun Y H,Green A,et al.Role of Neisseria meningitidis luxS in cell-to-cell signaling and bacteremic infection.Infect Immun,2002,70(4):2245-2248
130 Kozlova E V,Popov V L,Sha J,et al.Mutation in the S-ribosylhomocysteinase(luxS)gene involved in quorum sensing affects biofilm formation and virulence in a clinical isolate of Aeromonas hydrophila.Microb Pathog,2008,45(5-6):343-354
131 Lyon W R,Madden J C,Levin J C,et al.Mutation of lugs affects growth and virulence factor expression in Streptococcus pyogenes.Mol Microbiol,2001,42(1):145-157
132 Stroeher U H,Paton A W,Ogunniyi A D,et al.Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model.Infect hnmun,2003,71(6):3206-3212
133 Sztajer H,Lemme A,Vilchez R,et al.Autoinducer-2-regulated genes in Streptococcus mutans UA 159 and global metabolic effect of the luxS mutation.J Bacteriol,2008,190(1):401-415
134 Osaki T,Hanawa T,Manzoku T,et al.Mutation of luxS affects motility and infectivity of Helicobacter pylori in gastric mucosa of a Mongolian gerbil model.J Med Microbiol,2006,55(11):1477-1485
135 Sela S,Frank S,Belausov E,et al.A Mutation in the luxS gene influences Listeria monocytogenes biofilm formation.Appl Environ Microbiol,2006,72(8):5653-5658
136 Merritt J,Qi F,Goodman S D,et al.Mutation of luxS affects biofilm formation in Streptococcus mutans.Infect Immun,2003,71(4):1972-1979
137 Schneider R,Lockatell C V,Johnson D,et al.Detection and mutation of a luxS-encoded autoinducer in Proteus mirabilis.Microbiology,2002,148(3):773-782
138 Manefield M,Rasmussen T B,Henzter M,et al.Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover.Microbiology,2002,148(4):1119-1127
139 Hentzer M,Wu H,Andersen J B,et al.Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors.EMBO J,2003,22(15):3803-3815
140 Wu H,Song Z,Hentzer M,et al.Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice.J Antimicrob Chemoth,2004,53(6):1054-1061
141 Ishida T,Ikeda T,Takiguchi N,et al.Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopcntylamides.Appl Environ Microbiol,2007,73(10):3183-3188
142 Hoffmann N,Lee B,Hentzer M,et al.Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudornonas aeruginosa and attenuates chronic P.aeruginosa lung infection in mice.Antimicrob Agents Ch,2007,51(10):3677-3687
143 Zheng F R,Sun X Q,Liu H Z,et al.Study on the distribution and expression of a DNA vaccine against lymphocystis disease virus in Japanese flounder(Paralichthys olivaceus).Aquaculture,2006,261(4):1128-1134
144 Manefield M,Rasmussen T B,Henzter M,et al.Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover.Microbiology,2002,148(4):1119-1127
145 Rasmussen T B,Sldndersoe M E,Bjarnsholt T,et al,Identity and effects of quorum-sensing inhibitors produced by Penicillium species.2005,Soc General Microbiol.1325-1340.
146 Bjarnsholt T,Jensen P O,Rasmussen T B,et al.,Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.2005,Soc General Microbiol.3873-3880.
147 Hoffmann N,Lee B,Hentzer M,et al.Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Psendomonas aeruginosa and attenuates chronic P.aeruginosa lung infection in Cftr(-/-) mice.Antimicrob Agents Chemoth,2007,51(10):3677-3687
148 Rasmussen T B,Bjarnsholt T,Skindersoe M E,et al.Screening for quorum-sensing inhibitors(QSI) by use of a novel genetic system,the QSI selector.J Bacteriol,2005,187(5):1799-1814