两株鳗弧菌全基因组序列测定及转录组比较分析
|
摘要
鳗弧菌是水产病害中最常见的细菌病原,可感染鱼虾贝等多种水生动物,对养殖业造成巨大经济损失。鳗弧菌的基因组尚未阐明。本文开展了临床致病鳗弧菌株M3(血清型O1)和非致病标准菌株ATCC43308(血清型O4)的全基因组序列测定、基因组和转录组比较分析,为从整体了解鳗弧菌的生态、生理及致病机制打下基础。
首先用Roche 454 FLX Titanium测序得到的序列信息进行基因组骨架组装,然后用AB SOLID测序得到的序列信息进行高覆盖度测序补洞、scaffold搭建及延伸,完成拼接组装,对所获DNA序列进行了全面的生物信息学分析。分析结果显示:M3形成了23个scaffold,contig N50长度为334.6kb,基因组总G+C%含量为44.5%,预测并注释成功的CDS(coding sequence)总数为4009个,CDS平均长度为295aa;含48个tRNA和3个16s-23s-5s rRNA。ATCC43308有15个scaffold,N50长度为240.6 kb,基因组总G+C%含量为44.4%,有3820个注释过的CDS,平均长度为293aa,含有49个tRNA和3个16s-23s-5s rRNA。两株菌中注释的约27%CDS都是参与细胞的生命运动代谢过程,包括氨基酸转运和代谢,糖脂的代谢,DNA复制与修复,RNA转录与调控等;约10%CDS与毒力相关,包括粘附素,菌毛,分泌系统和转运系统等。两株菌存在较丰富的水平转移遗传元件,在M3和ATCC43308分别发现28和14个插入序列(IS)、21和19个Tn及18和9个prophage序列成份。
在详细分析两株菌基因组特征基础上,对它们进行了比较基因组研究,发现了鳗弧菌的代谢机制及致病性/毒力强弱的特征。M3基因组比ATCC43308大约230kb左右,而M3注释的CDS比ATCC43308多190个。其中差异基因较多的主要集中在参与信号传导过程、酶代谢、细胞菌膜形成和外膜蛋白以及假定蛋白和COG未包含的蛋白方面。两株菌中均发现了新的溶血素和金属蛋白酶及与T6SS相关基因。结果表明,ATCC43308缺失了荚膜多糖转运系统基因簇wza-wzb-wzc,使得荚膜多糖不能正常输送到胞外;M3中存在更多的有激活转录成份的IS序列,有利于更多基因的表达,并且在M3中发现了T3SS成份,而这些都与细菌的毒性密切相关,推测可能与M3致病性有关。
在转录组测序方面,对M3和ATCC43308基因表达量进行了比较,发现了191个表达有显著差异的基因,其中也包含与致病性相关的毒力因子。
由于鳗弧菌对养殖的严重危害,已有很多方法对其进行检测,如荧光PCR,免疫探针,血清学等。本文根据M3和ATCC43308以及NCBI上已公布的弧菌属全基因组序列,利用toxR-toxS两成份系统序列保守性设计了引物,建立了针对鳗弧菌、溶藻胶弧菌、哈氏弧菌、副溶血弧菌、创伤弧菌和霍乱弧菌六种水产常见病原微生物的多重PCR快速检测方法。结果表明,多重PCR引物特异性强,与其他弧菌及非弧菌无交叉反应,检测灵敏度为10-100 CFU,同时也对临床病料进行了检测,证明该多重PCR效果确实。
Vibrio anguillarum is a Gram-negative Gammaproteobacteria and can cause epidemic vibriosis in fish, bivalves and crustaceans, with the character as a hemorrhage septicemia to beget enormous economic losses. Whole genome sequencing of Vibrio anguillarum clinical pathogenic strain M3 and nonpathogenic ATCC43308 were perfomed with a combined strategy of using Roche 454 GS(FLX Titanium) pyrosequencing and AB SOLID mate-paired sequencing technology. In addition, based on the genomic information, transcriptomic profilings of M3 and ATCC43308 were analyzed by RNA-Seq tech. The sequence analysis of genome and transcriptome provided molecular-level understanding of genetic information and pathogenicity about Vibrio anguillarum.
Pathogenic M3 was made of 23 scaffolds, with the length of N50 with 240.6 kb, the content of G+C% with 44.5%, the amount of predicted and annotated CDS with 4009 and the average length of CDS with 295aa, with 48 tRNAs and 3 16s-23s-5s rRNAs. For nonpathgenic ATCC43308 with 15 scaffolds, the length of N50 334.6 kb, the G+C% 44.4%, CDS with 3820, the average length of CDS with 293aa, 49 tRNAs and 3 16s-23s-5s rRNAs. 27% of CDS participated in the metabolism, transport and replicate, transcription regulation et al. Some(about 10% CDS)were responsible for the pathogenesis containing secretion, adhesin and pilus et al.
Comparative genomics analysis among M3, ATCC43308 and other related available species described the detailed characteristics of the metabolism mechanism and pathogenesis about V. anguillarum. The strain ATCC43308 lacked a gene cluster, wza-wzb-wzc, which is responsible for the capsular polysaccharides transport through the cell membrane. Compared to ATCC43308, M3 were larger about 230 kb in genome seize, more 190 CDS in amount. The differences mainly pooled in the aspects including signal transduct, enzyme metabolism, cell envelope biogenesis and function unkown. For M3 and ATCC43308, more new hemolysin、metalloprotease and T6SS-related genes were found, some of which respected to the virulence of pathogen. Furthermore, compared to ATCC43308, more exterior sequences such as IS (28 vs 14) ,Tn(21 vs 19)and prophag(e18 vs 9), some of which are proved to be activators of other genes, were found in M3. We speculated that the components were necessary for M3 to cause diseases.
Comparative transcriptomic analysis of the two strains revealed 191 genes whose expression level differentiated remarkably.
Many methods were perfomed to detect the pathogen, such as real time PCR, immunoprobe and serological reaction. Based on the genome sequences of the two-component system toxR-toxS of genus Vibrio, six pairs of conserved primers to simultaneously detect main pathogenic vibrio including V. anguillarum, V. alginolyticus, V. harveyi, V. parahaemolyticus, V. vulnificus and V. cholerae were designed. The results showed that multiplex PCR have fairly specific to Vibrio, and nonspecific and cross-reaction were not found. Reaction sensitivity was 10~100 CFU. The detection for real samples also proved its reliability.
首先用Roche 454 FLX Titanium测序得到的序列信息进行基因组骨架组装,然后用AB SOLID测序得到的序列信息进行高覆盖度测序补洞、scaffold搭建及延伸,完成拼接组装,对所获DNA序列进行了全面的生物信息学分析。分析结果显示:M3形成了23个scaffold,contig N50长度为334.6kb,基因组总G+C%含量为44.5%,预测并注释成功的CDS(coding sequence)总数为4009个,CDS平均长度为295aa;含48个tRNA和3个16s-23s-5s rRNA。ATCC43308有15个scaffold,N50长度为240.6 kb,基因组总G+C%含量为44.4%,有3820个注释过的CDS,平均长度为293aa,含有49个tRNA和3个16s-23s-5s rRNA。两株菌中注释的约27%CDS都是参与细胞的生命运动代谢过程,包括氨基酸转运和代谢,糖脂的代谢,DNA复制与修复,RNA转录与调控等;约10%CDS与毒力相关,包括粘附素,菌毛,分泌系统和转运系统等。两株菌存在较丰富的水平转移遗传元件,在M3和ATCC43308分别发现28和14个插入序列(IS)、21和19个Tn及18和9个prophage序列成份。
在详细分析两株菌基因组特征基础上,对它们进行了比较基因组研究,发现了鳗弧菌的代谢机制及致病性/毒力强弱的特征。M3基因组比ATCC43308大约230kb左右,而M3注释的CDS比ATCC43308多190个。其中差异基因较多的主要集中在参与信号传导过程、酶代谢、细胞菌膜形成和外膜蛋白以及假定蛋白和COG未包含的蛋白方面。两株菌中均发现了新的溶血素和金属蛋白酶及与T6SS相关基因。结果表明,ATCC43308缺失了荚膜多糖转运系统基因簇wza-wzb-wzc,使得荚膜多糖不能正常输送到胞外;M3中存在更多的有激活转录成份的IS序列,有利于更多基因的表达,并且在M3中发现了T3SS成份,而这些都与细菌的毒性密切相关,推测可能与M3致病性有关。
在转录组测序方面,对M3和ATCC43308基因表达量进行了比较,发现了191个表达有显著差异的基因,其中也包含与致病性相关的毒力因子。
由于鳗弧菌对养殖的严重危害,已有很多方法对其进行检测,如荧光PCR,免疫探针,血清学等。本文根据M3和ATCC43308以及NCBI上已公布的弧菌属全基因组序列,利用toxR-toxS两成份系统序列保守性设计了引物,建立了针对鳗弧菌、溶藻胶弧菌、哈氏弧菌、副溶血弧菌、创伤弧菌和霍乱弧菌六种水产常见病原微生物的多重PCR快速检测方法。结果表明,多重PCR引物特异性强,与其他弧菌及非弧菌无交叉反应,检测灵敏度为10-100 CFU,同时也对临床病料进行了检测,证明该多重PCR效果确实。
Vibrio anguillarum is a Gram-negative Gammaproteobacteria and can cause epidemic vibriosis in fish, bivalves and crustaceans, with the character as a hemorrhage septicemia to beget enormous economic losses. Whole genome sequencing of Vibrio anguillarum clinical pathogenic strain M3 and nonpathogenic ATCC43308 were perfomed with a combined strategy of using Roche 454 GS(FLX Titanium) pyrosequencing and AB SOLID mate-paired sequencing technology. In addition, based on the genomic information, transcriptomic profilings of M3 and ATCC43308 were analyzed by RNA-Seq tech. The sequence analysis of genome and transcriptome provided molecular-level understanding of genetic information and pathogenicity about Vibrio anguillarum.
Pathogenic M3 was made of 23 scaffolds, with the length of N50 with 240.6 kb, the content of G+C% with 44.5%, the amount of predicted and annotated CDS with 4009 and the average length of CDS with 295aa, with 48 tRNAs and 3 16s-23s-5s rRNAs. For nonpathgenic ATCC43308 with 15 scaffolds, the length of N50 334.6 kb, the G+C% 44.4%, CDS with 3820, the average length of CDS with 293aa, 49 tRNAs and 3 16s-23s-5s rRNAs. 27% of CDS participated in the metabolism, transport and replicate, transcription regulation et al. Some(about 10% CDS)were responsible for the pathogenesis containing secretion, adhesin and pilus et al.
Comparative genomics analysis among M3, ATCC43308 and other related available species described the detailed characteristics of the metabolism mechanism and pathogenesis about V. anguillarum. The strain ATCC43308 lacked a gene cluster, wza-wzb-wzc, which is responsible for the capsular polysaccharides transport through the cell membrane. Compared to ATCC43308, M3 were larger about 230 kb in genome seize, more 190 CDS in amount. The differences mainly pooled in the aspects including signal transduct, enzyme metabolism, cell envelope biogenesis and function unkown. For M3 and ATCC43308, more new hemolysin、metalloprotease and T6SS-related genes were found, some of which respected to the virulence of pathogen. Furthermore, compared to ATCC43308, more exterior sequences such as IS (28 vs 14) ,Tn(21 vs 19)and prophag(e18 vs 9), some of which are proved to be activators of other genes, were found in M3. We speculated that the components were necessary for M3 to cause diseases.
Comparative transcriptomic analysis of the two strains revealed 191 genes whose expression level differentiated remarkably.
Many methods were perfomed to detect the pathogen, such as real time PCR, immunoprobe and serological reaction. Based on the genome sequences of the two-component system toxR-toxS of genus Vibrio, six pairs of conserved primers to simultaneously detect main pathogenic vibrio including V. anguillarum, V. alginolyticus, V. harveyi, V. parahaemolyticus, V. vulnificus and V. cholerae were designed. The results showed that multiplex PCR have fairly specific to Vibrio, and nonspecific and cross-reaction were not found. Reaction sensitivity was 10~100 CFU. The detection for real samples also proved its reliability.
引文
[1] Actis LA, Fish W, Crosa JH, Kellerman K,Ellenberger S, et al. Characterization of Anguibactin, a novel siderophore from Vibrio anguillarum 775(pJM1). J Bacteriol, 1986,167:57-65
[2] Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA, Berg DE. Analyses ofthe cag pathogenicity island of Helicobacter pylori. Mol Microbiol, 1998, 28:37-53
[3] Attridge S R and Rowley D.The Role of the Flagellum in the Adherence of Vibrio cholerae . J Infect Dis. 1983,147: 864-872
[4] Ballister Er, LaiAH, Zuckermann Rn, ChengY, Mougou JD. In vitro self-assembly of tailorable nanotube from a simple protein building block. Proc NatlAcad Sci USA, 2008, 105: 3733-3738
[5] Bao Q, Tian Y, Li W. A complete sequence of the T tengcongensis genome. Genome Res, 2002, 12: 689-700
[6] Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129: 823-837
[7] Bauer A and R?rvik LM. A novel multiplex PCR for the identification of Vibrio parahaemolyticus, Vibrio cholerae and Vibrio vulnificus. Letters in Applied Microbiology, 2007, 45:371-375
[8] Berriman M, Pain A. Variety is the spice of eukaryotic life. Nat RevMicrobiol, 2007, 5: 660-661
[9] Besemer J, Lomsadze A and Borodovsky M. GeneMarkS: a self-training method for predicition of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. Nucleic Acids Research, 2001, 29: 2607-2618
[10] Bilodeau AL, Waldbieser GC, Terhune JS, et al. A real-time polymerase chain reaction assay of the bacterium Edwardsiella ictaluri in channel catfish. J Aquat Anim Health. 2003,15: 80-86
[11] Birzele F, Schaub J, Rust W, et al. Into the unknown: expression profiling without genome sequence information in CHO by next generation sequencing. Nucleic Acids Res, 2010, doi:10.1093/nar/gkq 116
[12] Blanco-Abad, Ansede-Bermejo V, Rodriguez-Gastro J, et al. Evaluation of different procedures for the optimized detection of vibrio parahaemolyticus in mussels and environmental samples. Int J Food Microbiol, 2009, 129: 229-236
[13] Bolotin A , Wincker P , Mauger S , et al . The complete genome sequence of thelactic acid bacterium Lactococcus lactis ssp. Lactis IL1403. Genome Research , 2001 , 11 :731 - 753.
[14] Bolotin A, Mauger S, Malarme K, Ehrlich SD, Sorokin A. Low-redundancy sequencing of the entire Lactococcus lactis IL1403 genome. Antonie Van Leeuwenhoek, 1999, 76:27-76
[15] Boulnois, G. and Roberts. Genetics of capsularpolysaccharide production in bacteria. Curr Top Microbiol Immunol, 1990, 150: 1-20
[16] Chandler, M. and Mahillon, J. Insertion Sequences Revisited Mobile DNA II Edited by N.L., Craig et al. ASM Press 2002, 305-366
[17] Charlier, D., Piette J., and Glansdorff N.. IS3 can function as a mobile promoter in E. coli. Nucleic Acids Res, 1982,10:5935-5948
[18] Cohen ST, Bro sch R, Parkh ill J, et al. Deciphering the biology of Mycobacterium T ubercu losis from the comp lete sequence. Nature, 1998, 393: 537 -544.
[19] Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D et al. Massive gene decay in the leprosy bacillus. Nature, 2001, 409: 1007-1011
[20] Collis FS, Green ED, Guttmacher AE and Guyer MS. A vision for the future of Cornelis GR. Yersinia type III secretion:send in the effectors. Cell Biol, 2002, 158: 401-408
[21] Cornelissen CN and Sparling PF. Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens. Mol Microbial, 1994, 14: 843-850
[22] Croxatto A, Lauritz J, Chen C, Milton DL. Vibrio anguillarum colonization of rainbow trout integument requires a DNA locus involved in exopolysaccharide transport and biosynthesis. Environ Microbiol, 2007 , 9: 370-82.
[23] David VA, Deutch AH, Pawiyk AD et al. Cloning,sequencing and expression of the gene encoding the extracellular neutral protease, vibriolysin of Vibrio proteolyticus. Gene, 1992, 112: 107-112
[24] Delcher AL, Bratke KA, Powers EC, and Salzberg SL. Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics (Advance online version) (2007)
[25] Denkin SM and Nelson DR. Regulation of Vibrio anguillarum empA metalloprotease expression and its role in virulence. Applied and Environmental Microbiology, 2004, 25:136
[26] Dilip KS, Finkelstein MB,Ginkelstein RA et al. Antibody against the capsule of Vibrio cholerae O139 protects against experiental challenge. Infect Immun, 1996, 64:343-345
[27] Dudley EG, Thomson NR, Parkhill J, Morin-N P, Nataro-J P. Proteomic and microarray charaterization of AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli. Mol Microbiol, 2006, 61: 1267-1282
[28] Dzidic S., V. Bedekovic. Horizontal gene transfer-emerging multidrug resistance in hospital bacteria. Acta Pharmacol Sin, 2003, 24: 519-526
[29] Fallarino A, Attridge SR, Manning PA, Focareta T. Cloning and characterization of a novel haemolysin in Vibrio cholerae O1 that does not directly contribute to the virulence of the organism.Microbiology. 2002, 148:2181–2189
[30] Filee J, Siguier P, Chandler M. Insertion sequence diversity in archaea. Microbiol Mol Biol Rev, 2007, 71:121-157
[31] Finlay, B. and S. Falkow. Common themes in microbial pathogenicity revised. Microbiol Mol Biol Rev, 1997, 61: 136-169
[32] Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science, 1995, 269: 496-512
[33] Forsyth R A, Haselbeck R J, Ohlsen K L, et a1. A genomewides strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol, 2002, 43: 1387-1400
[34] Fournier P, Paulus F, and Otten L. IS870 requires a 5'-CTAG-3' target sequence to generate the stop codon for its large ORF1. J Bacteriol, 1993, 175: 3151-3160
[35] Fux C. A., J. W. Costerton, P. S. Stewart, P. Stoodley. Survival strategies of infectious biofilms. Trends Microbiol, 2005, 131: 34-40
[36] Galan JE, Wolf-Watz H. Protein delivery into eukaryotic cells by type III secretion machines. Nature, 2006, 444:567-573
[37] Galas DJ and Chandler M. Bacterial insertion sequences. 1989, p. 109-162. In D. Berg and M. Howe. (ed.), Mobile DNA. American Society for Microbiology, Washington D.C genomics research. Nature, 2003, 42: 835-846
[38] Ghosh P. Process of protein transport by the type III secretion system. Microbiol, 2004, 68: 771-795
[39] Grim CJ, Zo, YG, Hasan, NA, Ali, A,Chowdhury,WB et al. RNA colony blot hybridization method for enumeration of culturable vibrio cholerae and vibrio mimicus bacteria. Applied environ microbiol, 2009, 75: 5439-5444
[40] Gustafsson C, Govindarajan S, Minshull J. Codon bias and heterologous protein expression. Trends Biotechnol, 2004, 22: 346-353
[41] Haiminen N, Feltus FA, Parida L. Assessing Pooled BAC and Whole Genome Shotgun Strategies for Assembly of Complex Genomes. BMC Genomics, 2011, 12: 194
[42] Han Y, Pang X et al. Comparative transcriptome analysis of Yersinia pestis in response to hyperosmotic and high-salinity stress. Res Micriobiol , 2005(a),156: 403- 415
[43] Han Y, Pang X et al. DNA microarray analysis of the heat- and cold-shock stimulons in Yersinia pestis. Microbes Infect, 2005(b), 7: 335-348
[44] Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Braslavsky I, et al. Single-molecule DNA sequencing of a viral genome. Science, 2008, 320: 106-109
[45] Hase CC and Finkelstein RA. Cloning and nucleitide sequence of the Vibrio cholerae hemagglutinin/protease (HA/protease) gene and construction of an HA/ protease-negative strain. J Bacterial, 1991, 173: 3311-3317
[46] Hirono I, Masuda T, Aoki T. Cloning and detection of the hemolysin gene of Vibrio anguillarum. Microbial Pathogenesis, 1996, 21:173-182
[47] Hirst LD and Ellis AE. Utilization of transferrin and salmon serum as sources of iron by typical and atypical strains of Aeromonas salmonicida. Microbiology, 1996, 142:1543-1550
[48] Holley RW, Apgar J, Everett GA, et al. Structure of a ribonucleic acid. Science, 1965, 147: 1462-1465
[49] Honda T and Finkelstein A. Purification and characterization of a haemolysin produced by Vibrio cholerae biotype E1 Tor: another toxic aubtance produced by cholera vibrios. Infect Immun, 1979, 26: 1020-1027
[50] Honda T and Lida T. The pathogenicity of Vibrio parahaemolyticus and the role of the thermostable direct haemolysin and related haemolysins. Rev Med Microbiol, 1993, 4: 106-113
[51] Iida T and Honda T. Hemolysins produced by vibrios. Journal of Toxicology-Toxin Reviews, 1997, 16:215-227
[52] Jiunn C, Fong N and Yildiz FH. The rbmBCDEF Gene Cluster Modulates Development of Rugose Colony Morphology and Biofilm Formation in Vibrio cholerae. J Bacterio, 2007, 2: 2319–2330
[53] Johnson DS, Mortzavi A, Myers RM, Wold B. Genome-wide mapping of in vivo protein-DNA interactions. Science, 2007, 316: 1497-1502
[54] Kanehisa M and Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res, 2000, 28: 27-30.
[55] Kanehisa M, Goto S, Furumichi M, Tanabe M, and Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res, 2010, 38: 355-360.
[56] Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, and Hirakawa M. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res, 2006, 34: 354-357.
[57] Karan McGee, Per Horstedt, Milton DL. Identification and characterization of additional flagellin genes from Vibrio anguillarum. J Bacteriol, 1996, 178: 5188-5198
[58] Karolis V, Pramod K R, Barbro L, Rimas V,et al. The metalloprotease PrtV from Vibrio cholerae Purification and properties . FEBS Journal, 2008 , 275:3167–3177
[59] Knaust A, Frosch M. Genome-based vaccines. Int J Med Microbiol, 2004, 294: 295-301
[60] Koga T. and Kawata T . Isolation and partial properties of a porin-like protein from Vibrio parahaemolyticus cell envelope. Microbiology and Immunology, 1983, 27: 861–867
[61] Kong R Y C,Lee S K Y,Law T W F,et al. Rapid detection of six types of bacterial pathogens in marine waters by multiplex PCR. Water Res, 2002, 36: 2802-2812.
[62] Kothary MH and Kreger AS..Purification a characterization of an elastolytic protease of Vibrio vulnificus. J Gen Microbiol, 1987, 133:1783-1791
[63] Lagesen K, Hallin P , R?dland E A, St?rfeldt HH, Rognes T. RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Research, 2007, 35: 3100-3108
[64] Lee SE, Shin SH, Kim YR, Shin DH,Chung SS, et al. Vibrio vulnificus has the transmembrane transcription activator ToxRS stimulating the expression of the hemolysin gene vvhA. J Bacteriol, 2000, 182: 3405-3415
[65] Li GY, Li J, Xiao P, Guo YH, Mo ZL. Detection of type III secretion gene as an indicator for pathogenic Edwardsiella tarda Lett Appl Microbiol, 2011, 52: 213-219
[66] Lin ZK, Kumagai K, Baba K, Mekalanos JJ, et al. Vibrio parahaemolyticus has a homolog of the Vibrio cholerae toxRS operon that mediates environmentally induced regulation of the thermostable direct hemolysin gene. J Bacteriol, 1993, 175: 3844- 3855
[67] Lister R, O`Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell, 2008, 133: 395-397
[68] Livny J, Teonad H, Livny M, Waldor MK. High-Throughput, Kingdom-Wide . Prediction and Annotation of Bacterial Non-Coding RNAs. PLOS ONE , 2008, 3: e3197
[69] Ludwig A and Goebel M. Haemolysins of Escherichia coli. In Mechanisms 544 of Virulence. ed. Sussman, M. pp. Cambridge, Cambridge University Press, 1997, 281-329
[70] Lun S, Perez-Casal J, Connor W, et a1. Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb Pathog, 2003, 34: 27-37
[71] Serhir B, Dubreuil D, Higglns R. Purification and characterization of a 52-kilodalton immunoglobulin G-binding protein from Streptococcus suis capsular type 2. J Bacteriol, 1995, 177: 3830-3836
[72] Lundin S, Stranneheim H, Pettersson E, Klevebring D, Lundeberg J. Increased throughput by parallelization of library preparation for massive sequencing. PLoS One, 2010 , 5: e10029
[73] MacDonell, MT, Swartz, et al. Ribosomal RNA phylogenies for the vibrio-enteric group of eubacteria. Microbiological Sciences, 1986, 3: 172-179
[74] Mahmud ZH, Neogi,SB, Kassu,A, Mai Huong,BT,Jahid, IK et al. Occurrence, seasonality and genetic diversity of vibrio vulnificus in coastal seaweeds and water along the Kii Channel, Japan. FEMS Microbiol, 2008, 64: 209-218
[75] Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet, 2008, 9: 387-402
[76] Marioni J C, Mason C E, Mane S M, et al. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res, 2008, 18: 1509-1517
[77] McGrath PT, Lee H, Zhang L, Iniesta AA, Hottes AK, et al. High-throughput identification of transcriptome start sites, conserved promoter motifs and predicted regulons. Nat Biotechnol, 2007, 25:584-592
[78] McInerney JO. GCUA (General Codon Usage Analysis). Bioinformatics, 1998, 14 :372-373.
[79] Michael Y, Galperin1, and Guy R. Cochrane. The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection. Nucleic Acids Research, 2011, 39: D1
[80] Miller VL and Mekalanos JJ . Synthesis of cholerae toxin is positively regulated at the transcriptional level by toxR.Proc. Natl.acad.Sci.USA, 1984, 81: 3471-3475
[81] Milton DL, Norqvist A, Wolf-Watz H. Cloning of a metallprotease gene involved in the virulence mechanism of Vibrio anguillarum. J Bacteriol, 1992, 174: 7235-7244
[82] Milton DL, Ronan O`Toole, Per Horstedt, Hans Wolf-Watz. Flagellin A is essential for the virulence mechanism of Vibrio anguillarum. J Bacteriol, 1996, 178: 1310-1319
[83] Misra S, Agrawal A, Liao WK, Choudhary A. Anatomy of a Hash-based Long Read Sequence Mapping Algorithm for Next Generation DNA Sequencing. Bioinformatics,. 2010, ePub
[84] Mo ZL, Chen SY, Zhang PJ. Properties of proteolytic toxin of Vibrio anguillirum from diseased flounder. Chin J Oceano Luminol, 2002, 20: 316-322
[85] Mo ZL, Guo DS, Mao YX, Ye XH, Zou YX, Xiao P et al. Identification and characterization of prtV gene in Vibrio anguillarum. Chinese Journal of Oceanology and Limnology, 2009, 1: 55-61
[86] Mo ZL,Tan XG, Xu YL, et al. A Vibrio anguillarum strain associated with ulcerative skin in cultured flounder, Paralichthys olivaceus. Chin J Oceano Luminol, 2001, 19: 319-326
[87] Mo ZL, Xiao P, Mao YX, et al. Construction and characterization of a live, attenuated esrB mutant of Edwardsiella tarda and its potential as a vaccine against the haemorrhagic septicaemia in turbot, Scophthamus maximus (L.). Fish and Shellfish Immunology, 2007, 23: 521-530
[88] Morin RD, O′ConnorMD, GriffithM, et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res, 2008, 18: 610-621
[89] Mortazavi A, Williams B A, McCue K, et al. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods, 2008, 5: 621-628
[90] Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman Al, Joachimiak CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science, 2006, 312: 1526-1530
[91] Mune CB. Production and properties of a haemolytic toxin by Vibrio anguillarum. Fish Diseases. Third Copraq Session. Edited by Ahne W. Springer-Verlag Berlin Heidelberg New York, 1980, 69-74
[92] Nagalakshmi U, Wang Z, Waern K, Shou C , Raha D , Gerstein M, et al. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science, 2008, 320: 1344-1349
[93] Neogi SB, Chowdhury N, Asakura M, Hinenoya A, Haldar S et al. a highly sensitive and specific multiplex PCR assay for simultaneous detection of Vibrio cholerae, vibrio parahaemolyticus and vibrio vulnificus. Letters in applied microbiology, 2010, 23: 214:218
[94] Nhung PH, Ohkusu K, Miyasaka J, Sun XS and Ezaki T. Rapid and specificidentification of 5 human pathogenic vibrio species by multiplex polymerase chain reaction targeted to dnaJ gene. Diagn Microbiol Infect Dis, 2007, 59: 271-275
[95] Nishina Y, Miyoshi S and Nagase AA, et al. Significant role of an exocellular protease in utilization of hem by Vibrio vulnificus. Infect Immun. 1992, 60: 2128-2132
[96] Norqvist A, Norrman B, Wolf-Watz H. Identification and characterization of a zinc metalloprotease associated with invasion by the fish pathogen Vibrio anguillarum. Infect Immun, 1990,58: 3731-3736
[97] Osorio CR and Klose KE. A region of the transmembrane regulatory protein ToxR that tethers the transcriptional activation domain to the cytoplasmic membrane displays wide divergence among Vibrio species. J Bacteriol, 2000, 182: 526-528
[98] Pallen MJ, Chaudhuri RR, Henderson IR. Genomicanalysisofsecretionsystems. Cur Opin Microbiol, 2003, 6: 519-527
[99] Panangala VS, Shoemaker CA, Van Santen VL, et al. Multiplex PCR for simultaneous detection of 3 bacterial fish pathogens, Flavobacterium columnare, Edwardsiella ictaluri and Aeromonas hydrophila. Dis Aquat Organ, 2007, 74:199-208
[100] Park PJ et al. ChiP-seq: advantages and challenges of a maturing techonology. Nat Rev Genet, 2009, 10: 669-680
[101] Parkhill J, Wren BW, Thomson NR, Titball RW, Holden MT, Prentice MB, Sebaihia M, James KD, Churcher C, Mungall KL et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature, 2001, 413: 523-527
[102] Passalacqua KD,Varadarajan A, Ondov BD, et al. Structure and complexity of a bacterial transcriptome. Journal of Bacteriology, 2009, 191: 3203-3211
[103] Pearce R and Roberts. Cloning and analysis of geneclusters for production of the Escherichia coli K10 and KS4antigens: identification of a new group of serA-linked capsulegene clusters. J Bacteriol,1995, 177:3992-3997
[104] Perkins TT, Kingsley RA, Fookes MC et al. A strand-specific RNA-Seq analysis of the transcriptome of the typhoid bacillus Salmonella typhi. PLOS Genetics, 2009, 5: e1000569
[105] Pizza M, Scarlato V, Masignani V et al. Identification of vaccine candidate against serogroup B meningococcus by whole genome sequencing. 2000, Science, 287: 1816 -1820
[106] Pukatzki S, Ma AT, Sturtevant D, et al. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci USA, 2006, 103: 1528-1533
[107] Pukatzki S, MaAT, Revel AT, Sturtevant D, Mekalanos JJ. Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-linksactin. Proc NatlAcad Sci USA, 2007, 104: 15508-15513
[108] Pushkarev D, Neff NF, Quake SR. Single-molecule sequencing of an individual human genome. Nat Biotechnol, 2009, 27: 847-852.
[109] Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine, 2001, 19: 2688-2691
[110] Rawlings ND, Morton FR & Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res, 2006, 34: D270–D272
[111] Reddington K, O'Grady J, Dorai-Raj S, Maher M, van Soolingen D, Barry T. Novel multiplex real-time PCR diagnostic assay for identification and differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis complex strains. J Clin Microbiol, 2011, 49: 651-657
[112] Reeves PR. Variation in O-antigens, niche-specific selection and bacterial populations. FEMS Microbiol Lett, 1992, 100: 509-516
[113] Reich KA and Schoolnik GK. The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcription activator ToxR. J Bacteriol, 1994 , 176: 3085-3088
[114] Roberts. Bacterial polysaccharides in sickness and inhealth. Microbiology, 1995, 141: 2023-2031.
[115] Rodkhum C, Stocrk HM, et al. Putative virulence related genes in vibrio anguillarum identified by random genome sequencing. J Infect Dis, 2006, 29: 157- 166
[116] Rodkhum C, Hirono I, Crosa JH, etal. Four novel hemolysin genes of Vibrio anguillarum and their virulence to rainbow trout. Micriobial Pathogenesis, 2005, 39: 109-119
[117] Rotem S and Pascale C. Prokaryotic transcriptomics:a new view on regulation, physiology and pathogenicity. Nature Reviews Genetics, 2009, 24: 2695
[118] Sachidanandam R, Weissman D, Schmidt SC, et al. A map of humangenome sequence variation containing 1142 million nucleotide polymorphisms. Nature, 2001, 409: 928- 933
[119] Sanger F, Brownlee GG, Barrell BG. A two-dimensional fractionation procedure for radioactive nucleotides. J Mol Biol, 1965, 13 : 373-398
[120] Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977, 74 :5463-5467
[121] Saroj S D, Shashidhar R, Karani M, et al . Dist ribution of Sal-monella pat hogenicity island (SPI)28 and SPI210 among different serotypes of Salmonella .actin. Proc NatlAcad Sci USA, 2007, 104: 15508-15513
[108] Pushkarev D, Neff NF, Quake SR. Single-molecule sequencing of an individual human genome. Nat Biotechnol, 2009, 27: 847-852.
[109] Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine, 2001, 19: 2688-2691
[110] Rawlings ND, Morton FR & Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res, 2006, 34: D270–D272
[111] Reddington K, O'Grady J, Dorai-Raj S, Maher M, van Soolingen D, Barry T. Novel multiplex real-time PCR diagnostic assay for identification and differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis complex strains. J Clin Microbiol, 2011, 49: 651-657
[112] Reeves PR. Variation in O-antigens, niche-specific selection and bacterial populations. FEMS Microbiol Lett, 1992, 100: 509-516
[113] Reich KA and Schoolnik GK. The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcription activator ToxR. J Bacteriol, 1994 , 176: 3085-3088
[114] Roberts. Bacterial polysaccharides in sickness and inhealth. Microbiology, 1995, 141: 2023-2031.
[115] Rodkhum C, Stocrk HM, et al. Putative virulence related genes in vibrio anguillarum identified by random genome sequencing. J Infect Dis, 2006, 29: 157- 166
[116] Rodkhum C, Hirono I, Crosa JH, etal. Four novel hemolysin genes of Vibrio anguillarum and their virulence to rainbow trout. Micriobial Pathogenesis, 2005, 39: 109-119
[117] Rotem S and Pascale C. Prokaryotic transcriptomics:a new view on regulation, physiology and pathogenicity. Nature Reviews Genetics, 2009, 24: 2695
[118] Sachidanandam R, Weissman D, Schmidt SC, et al. A map of humangenome sequence variation containing 1142 million nucleotide polymorphisms. Nature, 2001, 409: 928- 933
[119] Sanger F, Brownlee GG, Barrell BG. A two-dimensional fractionation procedure for radioactive nucleotides. J Mol Biol, 1965, 13 : 373-398
[120] Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977, 74 :5463-5467
[121] Saroj S D, Shashidhar R, Karani M, et al . Dist ribution of Sal-monella pat hogenicity island (SPI)28 and SPI210 among different serotypes of Salmonella .
[135] Susanne S, Vítor AP, Martins S, Daniela B, Thomas B, Martina B, et al. Genome sequence of the ubiquitous hydrocarbon-degrading marine bacterium Alcanivorax borkumensis. Nature Biotechnology , 2006, 24: 997 - 1004
[136] Tang F, Barbacioru C, W ang Y, et a.l mRNA-S eq whole-transcriptome analysis of a s ingle cell Nature Methods, 2009, 6: 377-382
[137] Tang J Q, Wang C J, Feng Y J, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis Serotype 2. PLoS Med, 2006, 3: 668-676
[138] Tarr CL, Patel JS, Puhr ND, Sowers EG, Bopp CAand Strockbine NA. Identification of Vibrio isolates by a multiplex PCR assay and rpoB sequence determination. J Clin Microbiol, 2007, 45:134–140.
[139] Tatusov RL, Koonin EV, Lipman DJ. A genomic perspective on protein families. Science, 1997, 278: 631-637.
[140] Theresa M. Wizemann, Jon H. Heinrichs, John E. Adamou, Alice L. Erwin, et al. Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against Streptococcus pneumoniae. Infection and Immunity, 2001, 69: 1593- 1598
[141] Thompson F L, Thompson C C, Dias G M, et al. The genus Listonella MacDonell and Colwell 1986 is a later heterotypic synonym of the genus Vibrio Pacini 1854 (Approved Lists 1980) - A taxonomic opinion. International J of Systmetic and Evolutionary Microbiology, 2011: doi:ijs.0.030015
[142] Thompson FL, Gevers D, Thompson CC,Dawyndt P , Naser S et al. phylogeny and molecular identification of vibrios on the basis of multilocus sequence analysis. Appl Environ Microbiol, 2005, 71: 5107-5115
[143] Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, et al.The Listeria transcriptional landscape from saprophytism to virulence. Nature, 2009, 459: 950-956
[144] Torres C ,Tsiodras S , Gold HS , et al . Restoration of vancomycin susceptibility in Enterococcus faecalis by antiresistance determinant gene transfer. Antimicrob A gents Chemother, 2001, 45: 973.
[145] Villamil L, Figueras A, Novoa. Immunomodulatory effects of nisin in turbot (Scophthalmus maximus L). Fish&Shellfish Immunology, 2003, 14: 157-169
[146] Vuddhakul V, Nakai T, Matsumoto C, et al. Analysis of gyrB and toxR gene sequences of Vibrio hollisae and development of gyrB and toxR-targeted PCR methods for isolation of V. hollisae from the environment and its identification. Appl Environ Microbiol, 2000, 66: 3506-3514
[147] Wang L, Feng Z, Wang X, et al. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics, 2010, 26: 136-138
[148] Wang SY, Lauritz J, Jass J, Milton DL. A ToxR Homolog from Vibrio anguillarum Serotype O1 regulates its Production,Bile Resistance,and Biofilm Formation. J Bacteriol, 2002, 184: 1630-1639
[149] Wang SY, Lauritz J, Jass J, Milton DL. Role for the major outer membrane protein from Vibrio anguillarum in bile resistance and biofilm formation Microbiology, 2003, 149: 1061-1071
[150] WangYD, Zhao S, Hill CW. Rhs elements comprise three subfamilies which diverged prior to acquisition by Escherichia coli. J bacteriol, 1998, 180: 4102-4110
[151] Wassenaar TM and Gaastra W. Bacterial virulence: can we draw the line? FEMS Microbiol Lett, 2001, 201, 1-7
[152] Wertheimer AM, Verweij W, Chen Q, Crosa LM, et al. Characterization of the angR gene of Vibrio anguillarum essential role in virulence. Infect Immun, 1999, 67: 6494-6590
[153] Wilhelm BT, Marguerat S, Watt Schubert S, Wood V, Goodhead I, Christopher J. et al. Dynamic repertoire of a eukaryotic transcriptome surved at single nucleotide resolution. Nature, 2008,453: 1239-1243
[154] Williams ML and Lawrence ML. Verification of an Edwardsiella ictaluri-specific diagnostic PCR. Lett Appli Microbiol, 2009, 50:153-157
[155] Williams SG, Varcoe LT, Attredge SR, Manning PA. Vibrio cholerae Hcp,a secreted protein co-regulated with HlyA. Infect Immun, 1996, 64: 283-289
[156] Wolska KI. Horizontal DNA transfer between bacteria in the environment. Acta Microbiol Pol, 2003, 52: 233-243
[157] Wurtzel O, et al. A single-base resolution map of an archaeal transcriptome. Genome Res, 2009 , doi:10.1101/gr.100396.109
[158] Yamamoto K, Wright AC, Kaper JB, et al. The cytolysin gene of Vibrio vulnificus: sequence and relationship to the Vibrio cholerae E1 Tor hemolysin gene. Infect Immun, 1990, 58: 2706-2709
[159] Yang J, Chen LH, Sun LL, Yu J and Jin Q. VFDB 2008 release: an enhanced web-based resource for comparative pathogenomics. Nucleic Acids Res, 2008 36 (Database issue): D539-D542
[160] Yang X, Wu Q, Zhang J, Xu X. Rapid detection method of three types of bacterial pathogens in aquatic products established by multiplex PCR. Wei Sheng Yan Jiu, 2008, 37: 602-5
[161] Yoder-Himes DR, Chain PS, Zhu Y, et al. Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing. Proc Nat Acid Sci USA, 2009, 106: 3976-3981
[162] Zaghloul L, Tang C, Chin HY, Bek EJ, et al. The distribution of insertion sequences in the genome of Shigella flexneri strain 2457T. FEMS Microbiol Lett, 2007, 277: 197-204
[163] Zerillo MM, Vansluys MA, Camargo LEA et al. Characterizaiton of new IS elements and studies of their dispersion in two subspecies of Leifsonia xyli. BMC Microbial, 2008, 8:127
[164] Zhang XH and Austin B. Haemolysins in Vibrio species. J Appl Microbiol , 2005 , 98:256
[165] Zheng J, Leung KY. Dissection of a type VI secretion system in Edwardsiella tarda. Moleculr Microbiol, 2007, 66: 1192-1206
[166]白方方.哈维氏弧菌的密度感应系统及其信号干扰研究. 2007,中国海洋大学硕士学位论文
[167]包其郁,杨焕明.原核生物基因组DNA链组成的非对称性.微生物学报, 2002,42:755-761
[168]陈吉祥,刘霜,李筠,等.一种致病性鳗弧菌胞外蛋白酶的分离纯化及性质.中国水产科学, 2002, 9: 318-322
[169]陈师勇,莫照兰,张振冬等.鳗弧菌胞外产物中致病因子的分离纯化及性质研究.高技术通讯,12:96-101
[170]陈师勇.鳗弧菌主要致病因子的研究. 2003,中国科学院研究生院博士学位论文
[171]崔艳华,徐德昌,曲晓军.乳酸菌基因组学研究进展.生物信息学,
[172]邓显文,谢芝勋,谢志勤,刘加波,庞耀珊,谢丽基.多重聚合酶链反应快速检测嗜水气单胞菌和爱德华菌.中国人兽共患病学报, 2008, 24:752-755
[173]贺晓龙.霍乱弧菌及副溶血弧菌复合PCR检测方法的建立.青海大学学报(自然科学版), 2006, 24: 59-63
[174]解增言,林俊华,谭军,舒坤贤. DNA测序技术的发展历史与最新进展.生物技术通讯, 2010, 8: 64-71
[175]雷雾霖.新世纪我国海水鱼类繁养殖发展趋势和战略.现代渔业信息, 2000, 15 :1-5
[176]李润花,贾宝财.生物信息学在生物医学与药物开发中的应用.食品工程, 2010, 2: 16-20
[177]刘倩倩.创伤弧菌金属蛋白酶的研究进展.微生物学免疫学进展, 2009,37:66-70
[178]刘晓颖.微生物基因组与抗微生物药物的发展.国外医学-流行病学与传染病学分册, 2002, 29:138-142
[179]陆吉虎,李槿年,张传亮.病原弧菌毒素共调菌毛研究进展.动物医学进展, 2007, 28 :55258
[180]栾晓燕.副溶血弧菌的多样性、检测及其金属蛋白酶的研究. 2007,中国海洋大学硕士学位论文
[181]庞玲玲.哈维氏弧菌毒力相关基因的筛查及快速检测技术研究. 2007,中国海洋大学硕士学位论文
[182]乔纳森·佩夫斯纳编著.《生物信息学与功能基因组学》.化学工业出版社出版, 2006年6月1日第1版
[183]邱宁.苏云金芽孢杆菌YBT-1520基因组中插入序列组的研究. 2010,华中农业大学博士学位论文
[184]王斌.基于RNA-Seq技术的米曲霉RIB40转录组学研究. 2010,华南理工大学博士学位论文
[185]王芳平,李宏,刘国庆,李瑞芳.密码对的偏爱与基因组进化的相关性分析.生物信息学,2009,7:150-156
[186]王淑娴,张晓华,孙铂光,陈吉祥.不同海洋弧菌中5类溶血素基因的分布及其与溶血活性和磷脂酶活性的相关性.中国水产科学. 2007, 14:570-579
[187]王曦,汪小我,王立坤,冯智星,张学工.新一代高通量RNA测序数据的处理与分析.生物化学与生物物理进展, 2010, 37: 834~846
[188]王佐广,温绍君,吴兆苏.药物基因组学与药物的疗效.药物流行病学杂志, 2001, 10: 89-94
[189]魏武.重要病原微生物比较基因组研究的生物信息学方法和应用. 2007,中国科学院研究生院博士学位论文
[190]闻玉梅.微生物基因组研究进展及其意义.中华微生物学与免疫学杂志, 1999, 19: 353-356
[191]吴佳妍,肖景发,张若思,于军. DNA测序技术引领中国基因组科学走向未来.中国科学, 2010, 40: 1169-1172
[192]吴乃虎.基因工程原理(第二版).科学出版社, 2003
[193]谢建平,乐军,王洪海.利用微生物基因组开发新型抗生物.药物学报医学分册, 2002, 29:138-142
[194]杨佳银.迟缓爱德华氏菌基因组fosmid文库的构建、opp基因簇的克隆及aroA基因缺失突变株的构建. 2008,中国科学院研究生院硕士学位论文
[195]杨雷.副溶血弧菌的体外比较转录组学研究. 2009,中国医科科学院博士学位论文
[196]于聘飞,王英,葛芹玉.高通量DNA测序技术及其应用进展.南京晓庄学院学报, 2010,3: 1-5
[197]原志伟,朱国强.细菌V型分泌系统研究进展.生物技术通讯, 2007, 18:129-132
[198]岳立广,朱晶等.基于微生物基因组序列开发疫苗的研究进展与分析. 2007, 35: 69-75
[199]郑国兴,沈亚林,李何.中国对虾病原菌(鳗弧菌)的研究.水产学报,1990, 1:1-3
[200]周永运,徐建国肠道病原菌的三型分泌系统与侵袭.中国人兽共患病杂志,2003, 19:102-106
[201]邹玉霞.大菱鲆致病菌的分离鉴定和鳗弧菌溶血素基因的克隆、突变和表达. 2004,中国科学院研究生院博士学位论文
[2] Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA, Berg DE. Analyses ofthe cag pathogenicity island of Helicobacter pylori. Mol Microbiol, 1998, 28:37-53
[3] Attridge S R and Rowley D.The Role of the Flagellum in the Adherence of Vibrio cholerae . J Infect Dis. 1983,147: 864-872
[4] Ballister Er, LaiAH, Zuckermann Rn, ChengY, Mougou JD. In vitro self-assembly of tailorable nanotube from a simple protein building block. Proc NatlAcad Sci USA, 2008, 105: 3733-3738
[5] Bao Q, Tian Y, Li W. A complete sequence of the T tengcongensis genome. Genome Res, 2002, 12: 689-700
[6] Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129: 823-837
[7] Bauer A and R?rvik LM. A novel multiplex PCR for the identification of Vibrio parahaemolyticus, Vibrio cholerae and Vibrio vulnificus. Letters in Applied Microbiology, 2007, 45:371-375
[8] Berriman M, Pain A. Variety is the spice of eukaryotic life. Nat RevMicrobiol, 2007, 5: 660-661
[9] Besemer J, Lomsadze A and Borodovsky M. GeneMarkS: a self-training method for predicition of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. Nucleic Acids Research, 2001, 29: 2607-2618
[10] Bilodeau AL, Waldbieser GC, Terhune JS, et al. A real-time polymerase chain reaction assay of the bacterium Edwardsiella ictaluri in channel catfish. J Aquat Anim Health. 2003,15: 80-86
[11] Birzele F, Schaub J, Rust W, et al. Into the unknown: expression profiling without genome sequence information in CHO by next generation sequencing. Nucleic Acids Res, 2010, doi:10.1093/nar/gkq 116
[12] Blanco-Abad, Ansede-Bermejo V, Rodriguez-Gastro J, et al. Evaluation of different procedures for the optimized detection of vibrio parahaemolyticus in mussels and environmental samples. Int J Food Microbiol, 2009, 129: 229-236
[13] Bolotin A , Wincker P , Mauger S , et al . The complete genome sequence of thelactic acid bacterium Lactococcus lactis ssp. Lactis IL1403. Genome Research , 2001 , 11 :731 - 753.
[14] Bolotin A, Mauger S, Malarme K, Ehrlich SD, Sorokin A. Low-redundancy sequencing of the entire Lactococcus lactis IL1403 genome. Antonie Van Leeuwenhoek, 1999, 76:27-76
[15] Boulnois, G. and Roberts. Genetics of capsularpolysaccharide production in bacteria. Curr Top Microbiol Immunol, 1990, 150: 1-20
[16] Chandler, M. and Mahillon, J. Insertion Sequences Revisited Mobile DNA II Edited by N.L., Craig et al. ASM Press 2002, 305-366
[17] Charlier, D., Piette J., and Glansdorff N.. IS3 can function as a mobile promoter in E. coli. Nucleic Acids Res, 1982,10:5935-5948
[18] Cohen ST, Bro sch R, Parkh ill J, et al. Deciphering the biology of Mycobacterium T ubercu losis from the comp lete sequence. Nature, 1998, 393: 537 -544.
[19] Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D et al. Massive gene decay in the leprosy bacillus. Nature, 2001, 409: 1007-1011
[20] Collis FS, Green ED, Guttmacher AE and Guyer MS. A vision for the future of Cornelis GR. Yersinia type III secretion:send in the effectors. Cell Biol, 2002, 158: 401-408
[21] Cornelissen CN and Sparling PF. Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens. Mol Microbial, 1994, 14: 843-850
[22] Croxatto A, Lauritz J, Chen C, Milton DL. Vibrio anguillarum colonization of rainbow trout integument requires a DNA locus involved in exopolysaccharide transport and biosynthesis. Environ Microbiol, 2007 , 9: 370-82.
[23] David VA, Deutch AH, Pawiyk AD et al. Cloning,sequencing and expression of the gene encoding the extracellular neutral protease, vibriolysin of Vibrio proteolyticus. Gene, 1992, 112: 107-112
[24] Delcher AL, Bratke KA, Powers EC, and Salzberg SL. Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics (Advance online version) (2007)
[25] Denkin SM and Nelson DR. Regulation of Vibrio anguillarum empA metalloprotease expression and its role in virulence. Applied and Environmental Microbiology, 2004, 25:136
[26] Dilip KS, Finkelstein MB,Ginkelstein RA et al. Antibody against the capsule of Vibrio cholerae O139 protects against experiental challenge. Infect Immun, 1996, 64:343-345
[27] Dudley EG, Thomson NR, Parkhill J, Morin-N P, Nataro-J P. Proteomic and microarray charaterization of AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli. Mol Microbiol, 2006, 61: 1267-1282
[28] Dzidic S., V. Bedekovic. Horizontal gene transfer-emerging multidrug resistance in hospital bacteria. Acta Pharmacol Sin, 2003, 24: 519-526
[29] Fallarino A, Attridge SR, Manning PA, Focareta T. Cloning and characterization of a novel haemolysin in Vibrio cholerae O1 that does not directly contribute to the virulence of the organism.Microbiology. 2002, 148:2181–2189
[30] Filee J, Siguier P, Chandler M. Insertion sequence diversity in archaea. Microbiol Mol Biol Rev, 2007, 71:121-157
[31] Finlay, B. and S. Falkow. Common themes in microbial pathogenicity revised. Microbiol Mol Biol Rev, 1997, 61: 136-169
[32] Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science, 1995, 269: 496-512
[33] Forsyth R A, Haselbeck R J, Ohlsen K L, et a1. A genomewides strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol, 2002, 43: 1387-1400
[34] Fournier P, Paulus F, and Otten L. IS870 requires a 5'-CTAG-3' target sequence to generate the stop codon for its large ORF1. J Bacteriol, 1993, 175: 3151-3160
[35] Fux C. A., J. W. Costerton, P. S. Stewart, P. Stoodley. Survival strategies of infectious biofilms. Trends Microbiol, 2005, 131: 34-40
[36] Galan JE, Wolf-Watz H. Protein delivery into eukaryotic cells by type III secretion machines. Nature, 2006, 444:567-573
[37] Galas DJ and Chandler M. Bacterial insertion sequences. 1989, p. 109-162. In D. Berg and M. Howe. (ed.), Mobile DNA. American Society for Microbiology, Washington D.C genomics research. Nature, 2003, 42: 835-846
[38] Ghosh P. Process of protein transport by the type III secretion system. Microbiol, 2004, 68: 771-795
[39] Grim CJ, Zo, YG, Hasan, NA, Ali, A,Chowdhury,WB et al. RNA colony blot hybridization method for enumeration of culturable vibrio cholerae and vibrio mimicus bacteria. Applied environ microbiol, 2009, 75: 5439-5444
[40] Gustafsson C, Govindarajan S, Minshull J. Codon bias and heterologous protein expression. Trends Biotechnol, 2004, 22: 346-353
[41] Haiminen N, Feltus FA, Parida L. Assessing Pooled BAC and Whole Genome Shotgun Strategies for Assembly of Complex Genomes. BMC Genomics, 2011, 12: 194
[42] Han Y, Pang X et al. Comparative transcriptome analysis of Yersinia pestis in response to hyperosmotic and high-salinity stress. Res Micriobiol , 2005(a),156: 403- 415
[43] Han Y, Pang X et al. DNA microarray analysis of the heat- and cold-shock stimulons in Yersinia pestis. Microbes Infect, 2005(b), 7: 335-348
[44] Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Braslavsky I, et al. Single-molecule DNA sequencing of a viral genome. Science, 2008, 320: 106-109
[45] Hase CC and Finkelstein RA. Cloning and nucleitide sequence of the Vibrio cholerae hemagglutinin/protease (HA/protease) gene and construction of an HA/ protease-negative strain. J Bacterial, 1991, 173: 3311-3317
[46] Hirono I, Masuda T, Aoki T. Cloning and detection of the hemolysin gene of Vibrio anguillarum. Microbial Pathogenesis, 1996, 21:173-182
[47] Hirst LD and Ellis AE. Utilization of transferrin and salmon serum as sources of iron by typical and atypical strains of Aeromonas salmonicida. Microbiology, 1996, 142:1543-1550
[48] Holley RW, Apgar J, Everett GA, et al. Structure of a ribonucleic acid. Science, 1965, 147: 1462-1465
[49] Honda T and Finkelstein A. Purification and characterization of a haemolysin produced by Vibrio cholerae biotype E1 Tor: another toxic aubtance produced by cholera vibrios. Infect Immun, 1979, 26: 1020-1027
[50] Honda T and Lida T. The pathogenicity of Vibrio parahaemolyticus and the role of the thermostable direct haemolysin and related haemolysins. Rev Med Microbiol, 1993, 4: 106-113
[51] Iida T and Honda T. Hemolysins produced by vibrios. Journal of Toxicology-Toxin Reviews, 1997, 16:215-227
[52] Jiunn C, Fong N and Yildiz FH. The rbmBCDEF Gene Cluster Modulates Development of Rugose Colony Morphology and Biofilm Formation in Vibrio cholerae. J Bacterio, 2007, 2: 2319–2330
[53] Johnson DS, Mortzavi A, Myers RM, Wold B. Genome-wide mapping of in vivo protein-DNA interactions. Science, 2007, 316: 1497-1502
[54] Kanehisa M and Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res, 2000, 28: 27-30.
[55] Kanehisa M, Goto S, Furumichi M, Tanabe M, and Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res, 2010, 38: 355-360.
[56] Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, and Hirakawa M. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res, 2006, 34: 354-357.
[57] Karan McGee, Per Horstedt, Milton DL. Identification and characterization of additional flagellin genes from Vibrio anguillarum. J Bacteriol, 1996, 178: 5188-5198
[58] Karolis V, Pramod K R, Barbro L, Rimas V,et al. The metalloprotease PrtV from Vibrio cholerae Purification and properties . FEBS Journal, 2008 , 275:3167–3177
[59] Knaust A, Frosch M. Genome-based vaccines. Int J Med Microbiol, 2004, 294: 295-301
[60] Koga T. and Kawata T . Isolation and partial properties of a porin-like protein from Vibrio parahaemolyticus cell envelope. Microbiology and Immunology, 1983, 27: 861–867
[61] Kong R Y C,Lee S K Y,Law T W F,et al. Rapid detection of six types of bacterial pathogens in marine waters by multiplex PCR. Water Res, 2002, 36: 2802-2812.
[62] Kothary MH and Kreger AS..Purification a characterization of an elastolytic protease of Vibrio vulnificus. J Gen Microbiol, 1987, 133:1783-1791
[63] Lagesen K, Hallin P , R?dland E A, St?rfeldt HH, Rognes T. RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Research, 2007, 35: 3100-3108
[64] Lee SE, Shin SH, Kim YR, Shin DH,Chung SS, et al. Vibrio vulnificus has the transmembrane transcription activator ToxRS stimulating the expression of the hemolysin gene vvhA. J Bacteriol, 2000, 182: 3405-3415
[65] Li GY, Li J, Xiao P, Guo YH, Mo ZL. Detection of type III secretion gene as an indicator for pathogenic Edwardsiella tarda Lett Appl Microbiol, 2011, 52: 213-219
[66] Lin ZK, Kumagai K, Baba K, Mekalanos JJ, et al. Vibrio parahaemolyticus has a homolog of the Vibrio cholerae toxRS operon that mediates environmentally induced regulation of the thermostable direct hemolysin gene. J Bacteriol, 1993, 175: 3844- 3855
[67] Lister R, O`Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell, 2008, 133: 395-397
[68] Livny J, Teonad H, Livny M, Waldor MK. High-Throughput, Kingdom-Wide . Prediction and Annotation of Bacterial Non-Coding RNAs. PLOS ONE , 2008, 3: e3197
[69] Ludwig A and Goebel M. Haemolysins of Escherichia coli. In Mechanisms 544 of Virulence. ed. Sussman, M. pp. Cambridge, Cambridge University Press, 1997, 281-329
[70] Lun S, Perez-Casal J, Connor W, et a1. Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb Pathog, 2003, 34: 27-37
[71] Serhir B, Dubreuil D, Higglns R. Purification and characterization of a 52-kilodalton immunoglobulin G-binding protein from Streptococcus suis capsular type 2. J Bacteriol, 1995, 177: 3830-3836
[72] Lundin S, Stranneheim H, Pettersson E, Klevebring D, Lundeberg J. Increased throughput by parallelization of library preparation for massive sequencing. PLoS One, 2010 , 5: e10029
[73] MacDonell, MT, Swartz, et al. Ribosomal RNA phylogenies for the vibrio-enteric group of eubacteria. Microbiological Sciences, 1986, 3: 172-179
[74] Mahmud ZH, Neogi,SB, Kassu,A, Mai Huong,BT,Jahid, IK et al. Occurrence, seasonality and genetic diversity of vibrio vulnificus in coastal seaweeds and water along the Kii Channel, Japan. FEMS Microbiol, 2008, 64: 209-218
[75] Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet, 2008, 9: 387-402
[76] Marioni J C, Mason C E, Mane S M, et al. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res, 2008, 18: 1509-1517
[77] McGrath PT, Lee H, Zhang L, Iniesta AA, Hottes AK, et al. High-throughput identification of transcriptome start sites, conserved promoter motifs and predicted regulons. Nat Biotechnol, 2007, 25:584-592
[78] McInerney JO. GCUA (General Codon Usage Analysis). Bioinformatics, 1998, 14 :372-373.
[79] Michael Y, Galperin1, and Guy R. Cochrane. The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection. Nucleic Acids Research, 2011, 39: D1
[80] Miller VL and Mekalanos JJ . Synthesis of cholerae toxin is positively regulated at the transcriptional level by toxR.Proc. Natl.acad.Sci.USA, 1984, 81: 3471-3475
[81] Milton DL, Norqvist A, Wolf-Watz H. Cloning of a metallprotease gene involved in the virulence mechanism of Vibrio anguillarum. J Bacteriol, 1992, 174: 7235-7244
[82] Milton DL, Ronan O`Toole, Per Horstedt, Hans Wolf-Watz. Flagellin A is essential for the virulence mechanism of Vibrio anguillarum. J Bacteriol, 1996, 178: 1310-1319
[83] Misra S, Agrawal A, Liao WK, Choudhary A. Anatomy of a Hash-based Long Read Sequence Mapping Algorithm for Next Generation DNA Sequencing. Bioinformatics,. 2010, ePub
[84] Mo ZL, Chen SY, Zhang PJ. Properties of proteolytic toxin of Vibrio anguillirum from diseased flounder. Chin J Oceano Luminol, 2002, 20: 316-322
[85] Mo ZL, Guo DS, Mao YX, Ye XH, Zou YX, Xiao P et al. Identification and characterization of prtV gene in Vibrio anguillarum. Chinese Journal of Oceanology and Limnology, 2009, 1: 55-61
[86] Mo ZL,Tan XG, Xu YL, et al. A Vibrio anguillarum strain associated with ulcerative skin in cultured flounder, Paralichthys olivaceus. Chin J Oceano Luminol, 2001, 19: 319-326
[87] Mo ZL, Xiao P, Mao YX, et al. Construction and characterization of a live, attenuated esrB mutant of Edwardsiella tarda and its potential as a vaccine against the haemorrhagic septicaemia in turbot, Scophthamus maximus (L.). Fish and Shellfish Immunology, 2007, 23: 521-530
[88] Morin RD, O′ConnorMD, GriffithM, et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res, 2008, 18: 610-621
[89] Mortazavi A, Williams B A, McCue K, et al. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods, 2008, 5: 621-628
[90] Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman Al, Joachimiak CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science, 2006, 312: 1526-1530
[91] Mune CB. Production and properties of a haemolytic toxin by Vibrio anguillarum. Fish Diseases. Third Copraq Session. Edited by Ahne W. Springer-Verlag Berlin Heidelberg New York, 1980, 69-74
[92] Nagalakshmi U, Wang Z, Waern K, Shou C , Raha D , Gerstein M, et al. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science, 2008, 320: 1344-1349
[93] Neogi SB, Chowdhury N, Asakura M, Hinenoya A, Haldar S et al. a highly sensitive and specific multiplex PCR assay for simultaneous detection of Vibrio cholerae, vibrio parahaemolyticus and vibrio vulnificus. Letters in applied microbiology, 2010, 23: 214:218
[94] Nhung PH, Ohkusu K, Miyasaka J, Sun XS and Ezaki T. Rapid and specificidentification of 5 human pathogenic vibrio species by multiplex polymerase chain reaction targeted to dnaJ gene. Diagn Microbiol Infect Dis, 2007, 59: 271-275
[95] Nishina Y, Miyoshi S and Nagase AA, et al. Significant role of an exocellular protease in utilization of hem by Vibrio vulnificus. Infect Immun. 1992, 60: 2128-2132
[96] Norqvist A, Norrman B, Wolf-Watz H. Identification and characterization of a zinc metalloprotease associated with invasion by the fish pathogen Vibrio anguillarum. Infect Immun, 1990,58: 3731-3736
[97] Osorio CR and Klose KE. A region of the transmembrane regulatory protein ToxR that tethers the transcriptional activation domain to the cytoplasmic membrane displays wide divergence among Vibrio species. J Bacteriol, 2000, 182: 526-528
[98] Pallen MJ, Chaudhuri RR, Henderson IR. Genomicanalysisofsecretionsystems. Cur Opin Microbiol, 2003, 6: 519-527
[99] Panangala VS, Shoemaker CA, Van Santen VL, et al. Multiplex PCR for simultaneous detection of 3 bacterial fish pathogens, Flavobacterium columnare, Edwardsiella ictaluri and Aeromonas hydrophila. Dis Aquat Organ, 2007, 74:199-208
[100] Park PJ et al. ChiP-seq: advantages and challenges of a maturing techonology. Nat Rev Genet, 2009, 10: 669-680
[101] Parkhill J, Wren BW, Thomson NR, Titball RW, Holden MT, Prentice MB, Sebaihia M, James KD, Churcher C, Mungall KL et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature, 2001, 413: 523-527
[102] Passalacqua KD,Varadarajan A, Ondov BD, et al. Structure and complexity of a bacterial transcriptome. Journal of Bacteriology, 2009, 191: 3203-3211
[103] Pearce R and Roberts. Cloning and analysis of geneclusters for production of the Escherichia coli K10 and KS4antigens: identification of a new group of serA-linked capsulegene clusters. J Bacteriol,1995, 177:3992-3997
[104] Perkins TT, Kingsley RA, Fookes MC et al. A strand-specific RNA-Seq analysis of the transcriptome of the typhoid bacillus Salmonella typhi. PLOS Genetics, 2009, 5: e1000569
[105] Pizza M, Scarlato V, Masignani V et al. Identification of vaccine candidate against serogroup B meningococcus by whole genome sequencing. 2000, Science, 287: 1816 -1820
[106] Pukatzki S, Ma AT, Sturtevant D, et al. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci USA, 2006, 103: 1528-1533
[107] Pukatzki S, MaAT, Revel AT, Sturtevant D, Mekalanos JJ. Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-linksactin. Proc NatlAcad Sci USA, 2007, 104: 15508-15513
[108] Pushkarev D, Neff NF, Quake SR. Single-molecule sequencing of an individual human genome. Nat Biotechnol, 2009, 27: 847-852.
[109] Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine, 2001, 19: 2688-2691
[110] Rawlings ND, Morton FR & Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res, 2006, 34: D270–D272
[111] Reddington K, O'Grady J, Dorai-Raj S, Maher M, van Soolingen D, Barry T. Novel multiplex real-time PCR diagnostic assay for identification and differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis complex strains. J Clin Microbiol, 2011, 49: 651-657
[112] Reeves PR. Variation in O-antigens, niche-specific selection and bacterial populations. FEMS Microbiol Lett, 1992, 100: 509-516
[113] Reich KA and Schoolnik GK. The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcription activator ToxR. J Bacteriol, 1994 , 176: 3085-3088
[114] Roberts. Bacterial polysaccharides in sickness and inhealth. Microbiology, 1995, 141: 2023-2031.
[115] Rodkhum C, Stocrk HM, et al. Putative virulence related genes in vibrio anguillarum identified by random genome sequencing. J Infect Dis, 2006, 29: 157- 166
[116] Rodkhum C, Hirono I, Crosa JH, etal. Four novel hemolysin genes of Vibrio anguillarum and their virulence to rainbow trout. Micriobial Pathogenesis, 2005, 39: 109-119
[117] Rotem S and Pascale C. Prokaryotic transcriptomics:a new view on regulation, physiology and pathogenicity. Nature Reviews Genetics, 2009, 24: 2695
[118] Sachidanandam R, Weissman D, Schmidt SC, et al. A map of humangenome sequence variation containing 1142 million nucleotide polymorphisms. Nature, 2001, 409: 928- 933
[119] Sanger F, Brownlee GG, Barrell BG. A two-dimensional fractionation procedure for radioactive nucleotides. J Mol Biol, 1965, 13 : 373-398
[120] Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977, 74 :5463-5467
[121] Saroj S D, Shashidhar R, Karani M, et al . Dist ribution of Sal-monella pat hogenicity island (SPI)28 and SPI210 among different serotypes of Salmonella .actin. Proc NatlAcad Sci USA, 2007, 104: 15508-15513
[108] Pushkarev D, Neff NF, Quake SR. Single-molecule sequencing of an individual human genome. Nat Biotechnol, 2009, 27: 847-852.
[109] Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine, 2001, 19: 2688-2691
[110] Rawlings ND, Morton FR & Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res, 2006, 34: D270–D272
[111] Reddington K, O'Grady J, Dorai-Raj S, Maher M, van Soolingen D, Barry T. Novel multiplex real-time PCR diagnostic assay for identification and differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis complex strains. J Clin Microbiol, 2011, 49: 651-657
[112] Reeves PR. Variation in O-antigens, niche-specific selection and bacterial populations. FEMS Microbiol Lett, 1992, 100: 509-516
[113] Reich KA and Schoolnik GK. The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcription activator ToxR. J Bacteriol, 1994 , 176: 3085-3088
[114] Roberts. Bacterial polysaccharides in sickness and inhealth. Microbiology, 1995, 141: 2023-2031.
[115] Rodkhum C, Stocrk HM, et al. Putative virulence related genes in vibrio anguillarum identified by random genome sequencing. J Infect Dis, 2006, 29: 157- 166
[116] Rodkhum C, Hirono I, Crosa JH, etal. Four novel hemolysin genes of Vibrio anguillarum and their virulence to rainbow trout. Micriobial Pathogenesis, 2005, 39: 109-119
[117] Rotem S and Pascale C. Prokaryotic transcriptomics:a new view on regulation, physiology and pathogenicity. Nature Reviews Genetics, 2009, 24: 2695
[118] Sachidanandam R, Weissman D, Schmidt SC, et al. A map of humangenome sequence variation containing 1142 million nucleotide polymorphisms. Nature, 2001, 409: 928- 933
[119] Sanger F, Brownlee GG, Barrell BG. A two-dimensional fractionation procedure for radioactive nucleotides. J Mol Biol, 1965, 13 : 373-398
[120] Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977, 74 :5463-5467
[121] Saroj S D, Shashidhar R, Karani M, et al . Dist ribution of Sal-monella pat hogenicity island (SPI)28 and SPI210 among different serotypes of Salmonella .
[135] Susanne S, Vítor AP, Martins S, Daniela B, Thomas B, Martina B, et al. Genome sequence of the ubiquitous hydrocarbon-degrading marine bacterium Alcanivorax borkumensis. Nature Biotechnology , 2006, 24: 997 - 1004
[136] Tang F, Barbacioru C, W ang Y, et a.l mRNA-S eq whole-transcriptome analysis of a s ingle cell Nature Methods, 2009, 6: 377-382
[137] Tang J Q, Wang C J, Feng Y J, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis Serotype 2. PLoS Med, 2006, 3: 668-676
[138] Tarr CL, Patel JS, Puhr ND, Sowers EG, Bopp CAand Strockbine NA. Identification of Vibrio isolates by a multiplex PCR assay and rpoB sequence determination. J Clin Microbiol, 2007, 45:134–140.
[139] Tatusov RL, Koonin EV, Lipman DJ. A genomic perspective on protein families. Science, 1997, 278: 631-637.
[140] Theresa M. Wizemann, Jon H. Heinrichs, John E. Adamou, Alice L. Erwin, et al. Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against Streptococcus pneumoniae. Infection and Immunity, 2001, 69: 1593- 1598
[141] Thompson F L, Thompson C C, Dias G M, et al. The genus Listonella MacDonell and Colwell 1986 is a later heterotypic synonym of the genus Vibrio Pacini 1854 (Approved Lists 1980) - A taxonomic opinion. International J of Systmetic and Evolutionary Microbiology, 2011: doi:ijs.0.030015
[142] Thompson FL, Gevers D, Thompson CC,Dawyndt P , Naser S et al. phylogeny and molecular identification of vibrios on the basis of multilocus sequence analysis. Appl Environ Microbiol, 2005, 71: 5107-5115
[143] Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, et al.The Listeria transcriptional landscape from saprophytism to virulence. Nature, 2009, 459: 950-956
[144] Torres C ,Tsiodras S , Gold HS , et al . Restoration of vancomycin susceptibility in Enterococcus faecalis by antiresistance determinant gene transfer. Antimicrob A gents Chemother, 2001, 45: 973.
[145] Villamil L, Figueras A, Novoa. Immunomodulatory effects of nisin in turbot (Scophthalmus maximus L). Fish&Shellfish Immunology, 2003, 14: 157-169
[146] Vuddhakul V, Nakai T, Matsumoto C, et al. Analysis of gyrB and toxR gene sequences of Vibrio hollisae and development of gyrB and toxR-targeted PCR methods for isolation of V. hollisae from the environment and its identification. Appl Environ Microbiol, 2000, 66: 3506-3514
[147] Wang L, Feng Z, Wang X, et al. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics, 2010, 26: 136-138
[148] Wang SY, Lauritz J, Jass J, Milton DL. A ToxR Homolog from Vibrio anguillarum Serotype O1 regulates its Production,Bile Resistance,and Biofilm Formation. J Bacteriol, 2002, 184: 1630-1639
[149] Wang SY, Lauritz J, Jass J, Milton DL. Role for the major outer membrane protein from Vibrio anguillarum in bile resistance and biofilm formation Microbiology, 2003, 149: 1061-1071
[150] WangYD, Zhao S, Hill CW. Rhs elements comprise three subfamilies which diverged prior to acquisition by Escherichia coli. J bacteriol, 1998, 180: 4102-4110
[151] Wassenaar TM and Gaastra W. Bacterial virulence: can we draw the line? FEMS Microbiol Lett, 2001, 201, 1-7
[152] Wertheimer AM, Verweij W, Chen Q, Crosa LM, et al. Characterization of the angR gene of Vibrio anguillarum essential role in virulence. Infect Immun, 1999, 67: 6494-6590
[153] Wilhelm BT, Marguerat S, Watt Schubert S, Wood V, Goodhead I, Christopher J. et al. Dynamic repertoire of a eukaryotic transcriptome surved at single nucleotide resolution. Nature, 2008,453: 1239-1243
[154] Williams ML and Lawrence ML. Verification of an Edwardsiella ictaluri-specific diagnostic PCR. Lett Appli Microbiol, 2009, 50:153-157
[155] Williams SG, Varcoe LT, Attredge SR, Manning PA. Vibrio cholerae Hcp,a secreted protein co-regulated with HlyA. Infect Immun, 1996, 64: 283-289
[156] Wolska KI. Horizontal DNA transfer between bacteria in the environment. Acta Microbiol Pol, 2003, 52: 233-243
[157] Wurtzel O, et al. A single-base resolution map of an archaeal transcriptome. Genome Res, 2009 , doi:10.1101/gr.100396.109
[158] Yamamoto K, Wright AC, Kaper JB, et al. The cytolysin gene of Vibrio vulnificus: sequence and relationship to the Vibrio cholerae E1 Tor hemolysin gene. Infect Immun, 1990, 58: 2706-2709
[159] Yang J, Chen LH, Sun LL, Yu J and Jin Q. VFDB 2008 release: an enhanced web-based resource for comparative pathogenomics. Nucleic Acids Res, 2008 36 (Database issue): D539-D542
[160] Yang X, Wu Q, Zhang J, Xu X. Rapid detection method of three types of bacterial pathogens in aquatic products established by multiplex PCR. Wei Sheng Yan Jiu, 2008, 37: 602-5
[161] Yoder-Himes DR, Chain PS, Zhu Y, et al. Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing. Proc Nat Acid Sci USA, 2009, 106: 3976-3981
[162] Zaghloul L, Tang C, Chin HY, Bek EJ, et al. The distribution of insertion sequences in the genome of Shigella flexneri strain 2457T. FEMS Microbiol Lett, 2007, 277: 197-204
[163] Zerillo MM, Vansluys MA, Camargo LEA et al. Characterizaiton of new IS elements and studies of their dispersion in two subspecies of Leifsonia xyli. BMC Microbial, 2008, 8:127
[164] Zhang XH and Austin B. Haemolysins in Vibrio species. J Appl Microbiol , 2005 , 98:256
[165] Zheng J, Leung KY. Dissection of a type VI secretion system in Edwardsiella tarda. Moleculr Microbiol, 2007, 66: 1192-1206
[166]白方方.哈维氏弧菌的密度感应系统及其信号干扰研究. 2007,中国海洋大学硕士学位论文
[167]包其郁,杨焕明.原核生物基因组DNA链组成的非对称性.微生物学报, 2002,42:755-761
[168]陈吉祥,刘霜,李筠,等.一种致病性鳗弧菌胞外蛋白酶的分离纯化及性质.中国水产科学, 2002, 9: 318-322
[169]陈师勇,莫照兰,张振冬等.鳗弧菌胞外产物中致病因子的分离纯化及性质研究.高技术通讯,12:96-101
[170]陈师勇.鳗弧菌主要致病因子的研究. 2003,中国科学院研究生院博士学位论文
[171]崔艳华,徐德昌,曲晓军.乳酸菌基因组学研究进展.生物信息学,
[172]邓显文,谢芝勋,谢志勤,刘加波,庞耀珊,谢丽基.多重聚合酶链反应快速检测嗜水气单胞菌和爱德华菌.中国人兽共患病学报, 2008, 24:752-755
[173]贺晓龙.霍乱弧菌及副溶血弧菌复合PCR检测方法的建立.青海大学学报(自然科学版), 2006, 24: 59-63
[174]解增言,林俊华,谭军,舒坤贤. DNA测序技术的发展历史与最新进展.生物技术通讯, 2010, 8: 64-71
[175]雷雾霖.新世纪我国海水鱼类繁养殖发展趋势和战略.现代渔业信息, 2000, 15 :1-5
[176]李润花,贾宝财.生物信息学在生物医学与药物开发中的应用.食品工程, 2010, 2: 16-20
[177]刘倩倩.创伤弧菌金属蛋白酶的研究进展.微生物学免疫学进展, 2009,37:66-70
[178]刘晓颖.微生物基因组与抗微生物药物的发展.国外医学-流行病学与传染病学分册, 2002, 29:138-142
[179]陆吉虎,李槿年,张传亮.病原弧菌毒素共调菌毛研究进展.动物医学进展, 2007, 28 :55258
[180]栾晓燕.副溶血弧菌的多样性、检测及其金属蛋白酶的研究. 2007,中国海洋大学硕士学位论文
[181]庞玲玲.哈维氏弧菌毒力相关基因的筛查及快速检测技术研究. 2007,中国海洋大学硕士学位论文
[182]乔纳森·佩夫斯纳编著.《生物信息学与功能基因组学》.化学工业出版社出版, 2006年6月1日第1版
[183]邱宁.苏云金芽孢杆菌YBT-1520基因组中插入序列组的研究. 2010,华中农业大学博士学位论文
[184]王斌.基于RNA-Seq技术的米曲霉RIB40转录组学研究. 2010,华南理工大学博士学位论文
[185]王芳平,李宏,刘国庆,李瑞芳.密码对的偏爱与基因组进化的相关性分析.生物信息学,2009,7:150-156
[186]王淑娴,张晓华,孙铂光,陈吉祥.不同海洋弧菌中5类溶血素基因的分布及其与溶血活性和磷脂酶活性的相关性.中国水产科学. 2007, 14:570-579
[187]王曦,汪小我,王立坤,冯智星,张学工.新一代高通量RNA测序数据的处理与分析.生物化学与生物物理进展, 2010, 37: 834~846
[188]王佐广,温绍君,吴兆苏.药物基因组学与药物的疗效.药物流行病学杂志, 2001, 10: 89-94
[189]魏武.重要病原微生物比较基因组研究的生物信息学方法和应用. 2007,中国科学院研究生院博士学位论文
[190]闻玉梅.微生物基因组研究进展及其意义.中华微生物学与免疫学杂志, 1999, 19: 353-356
[191]吴佳妍,肖景发,张若思,于军. DNA测序技术引领中国基因组科学走向未来.中国科学, 2010, 40: 1169-1172
[192]吴乃虎.基因工程原理(第二版).科学出版社, 2003
[193]谢建平,乐军,王洪海.利用微生物基因组开发新型抗生物.药物学报医学分册, 2002, 29:138-142
[194]杨佳银.迟缓爱德华氏菌基因组fosmid文库的构建、opp基因簇的克隆及aroA基因缺失突变株的构建. 2008,中国科学院研究生院硕士学位论文
[195]杨雷.副溶血弧菌的体外比较转录组学研究. 2009,中国医科科学院博士学位论文
[196]于聘飞,王英,葛芹玉.高通量DNA测序技术及其应用进展.南京晓庄学院学报, 2010,3: 1-5
[197]原志伟,朱国强.细菌V型分泌系统研究进展.生物技术通讯, 2007, 18:129-132
[198]岳立广,朱晶等.基于微生物基因组序列开发疫苗的研究进展与分析. 2007, 35: 69-75
[199]郑国兴,沈亚林,李何.中国对虾病原菌(鳗弧菌)的研究.水产学报,1990, 1:1-3
[200]周永运,徐建国肠道病原菌的三型分泌系统与侵袭.中国人兽共患病杂志,2003, 19:102-106
[201]邹玉霞.大菱鲆致病菌的分离鉴定和鳗弧菌溶血素基因的克隆、突变和表达. 2004,中国科学院研究生院博士学位论文