胸膜肺炎放线杆菌内生质粒和温敏复制型质粒的研究
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摘要
胸膜肺炎放线杆菌(Actinobacillus pleuropneumoniae,APP)是巴氏杆菌科中重要的病原菌,它引起猪的一种高度接触性传染呼吸道疾病—猪传染性胸膜肺炎(porcinecontagious pleuropneumonia,PCP)。该病分布广泛,难以根除,给世界养猪业造成了巨大的经济损失。因此,预防和控制该疾病尤其重要。然而APP血清型众多(目前已经发现有15种血清型),并且不同血清型之间的交叉保护力较低,对该病的预防控制和治疗带来了极大的困难。而且许多国家用大量不同的抗生素来预防和治疗猪传染性胸膜肺炎,致使许多病原菌(包括APP)产生了极强的抗药性,这对该病的预防和治疗更是雪上加霜。现阶段,为了解决APP的预防和治疗问题,需要对APP的毒力因子、毒力相关因子以及膜蛋白和鞭毛等进行分子生物学研究。但研究这些基因和相关因子的前提是要具备相应的遗传操作工具,如穿梭载体,高效的突变体构建平台等,为技术支持。本文主要对APP的遗传操作工具的研究,包括以下两个方面内容:
1.胸膜肺炎放线杆菌内生质粒pHB0503分析
质粒pHB0503分离于2005年的胸膜肺炎放线杆菌地方分离菌株HB0503。大小为15.079kb,含有16个ORF,其中7个是抗性基因(sul2,catA3,aacC2,strA,strB',blaROB-1和aph(3)-I)。对这些抗性基因簇序列的生物信息分析,来研究该抗生素簇的进化和结构组成。实验数据分析表明该质粒可能在来源不同的质粒间,发生了同源重组而形成的。另外,RT-PCR实验证明:两处抗性基因簇的共转录,分别从sul2和bla_(ROB-1)启动子开始地。对该质粒的复制蛋白的分析,有可能在此基础上构建在APP中能稳定复制地穿梭载体和遗传操作系统,为进一步从分子生物学水平研究胸膜肺炎放线杆菌提供技术支持。而且对内生质粒抗性基因的研究,对临床抗生素的使用也有指导意义。
2.胸膜肺炎放线杆菌温敏复制型质粒的构建
PCR定向突变系统是新型的高效遗传操作体系,已经广泛应用于微生物学研究。构建该系统至少需要重组酶系统、抗性基因PCR模版、诱导型启动子、温敏复制型质粒等四大要件。本实验室已经拥有前三大要件,缺乏APP的温敏复制型质粒。为了构建一个APP的温敏复制型质粒,本研究以APP-E.coli穿梭质粒pJN105和pR318为出发质粒,采用低保真度PCR基因扩增和修复系统缺陷型E.coli感受态细胞基因克隆两种途径筛选温敏复制元件,为构建温敏复制载体奠定基础。
Actinobacillus pleuropneumoniae(APP),a member of the Pasteurellaceae family,is the causative agent of porcine contagious pleuropneumonia(PCP),which is worldwide epidemic and difficult to eradicate,and is responsible for substantial economic losses in the pig industry worldwide.Therefore,it is essential to prevent,control and treat this disease,but due to at least 15 distinct serotpyes and lack of cross-protection among them, this disease is dfficult to prevent and control.Moreover,the widespread use of antimicrobial agents to treat or prevent PCP,which force many pathogenic bacteria to become multidrug resistant bacteria,including APP.So it is more difficult to prevent and treat animal diseases.At present,in order to prevent and treat APP,we need to understand some knowledge about virulence factors,virulence associated factors,membrance proteins and flagellas in the level of molecular biology.However,the prerequisite condition of research on these genes is to possess some genetic operation tools,such as shuttle vector or high-efficency technology of constructing mutant.This study mainly focused on genetic operation tool,including two parts as below:
Isolation,sequencing and genetic characterization of A.pleuropneumoniae native plasmid pHB0503.Plasmid pHB0503 was extracted from Actinobacillus pleuropneumoniae HB0503,which was isolated in 2005.The complete 15.079 kb sequence of this plasmid,containing 16 ORFs,seven of which were associated with antibiotic resistance genes(sul2 catA3,aacC2,strA,strB',bla_(ROB-1) and aph(3)-I),was analyzed with regard to the organization and evolution.The experiment data indicated that pHB0503 arose through inter-plasmid recombination processes among other plasmids. In addition,co-transcription of the cluster of resistance genes from the promoter upstream of sul2 and bla_(ROB-1) was confirmed by RT-PCR.Then,the analysis of Rep protein may help us to construct stable shuttle vector or genetic tools,which is very useful for molecular biology research on APP.Moreover,the detection of antibiotic resistance genes could instruct the clinical use of antibiotic.
Construction of temperature-sensitive plasmids for A.pleuropneumoniae.PCR targeting system is a high-efficiency genetic modification system and has been widely used in research fields of microbiology.This system consists of four parts:recombinase systems,templates for PCR amplification of resistance gene,induced promoter and temperature- sensitive(TS) vector.At present,we already have possessed three parts.So the only element that we lack is TS vector.In order to construct a TS vector for APP,this study researched on a base of APP-E.coli shuttle vectors(pJN105 and pR318) and used two different kinds of methods(low-Fi PCR amplification method and the method involved in cloning genes into XL1-RED competence cell,which is deficient in primary DNA repair pathways) to construct it,which provided some supports to the further construction or research on TS vector.
1.胸膜肺炎放线杆菌内生质粒pHB0503分析
质粒pHB0503分离于2005年的胸膜肺炎放线杆菌地方分离菌株HB0503。大小为15.079kb,含有16个ORF,其中7个是抗性基因(sul2,catA3,aacC2,strA,strB',blaROB-1和aph(3)-I)。对这些抗性基因簇序列的生物信息分析,来研究该抗生素簇的进化和结构组成。实验数据分析表明该质粒可能在来源不同的质粒间,发生了同源重组而形成的。另外,RT-PCR实验证明:两处抗性基因簇的共转录,分别从sul2和bla_(ROB-1)启动子开始地。对该质粒的复制蛋白的分析,有可能在此基础上构建在APP中能稳定复制地穿梭载体和遗传操作系统,为进一步从分子生物学水平研究胸膜肺炎放线杆菌提供技术支持。而且对内生质粒抗性基因的研究,对临床抗生素的使用也有指导意义。
2.胸膜肺炎放线杆菌温敏复制型质粒的构建
PCR定向突变系统是新型的高效遗传操作体系,已经广泛应用于微生物学研究。构建该系统至少需要重组酶系统、抗性基因PCR模版、诱导型启动子、温敏复制型质粒等四大要件。本实验室已经拥有前三大要件,缺乏APP的温敏复制型质粒。为了构建一个APP的温敏复制型质粒,本研究以APP-E.coli穿梭质粒pJN105和pR318为出发质粒,采用低保真度PCR基因扩增和修复系统缺陷型E.coli感受态细胞基因克隆两种途径筛选温敏复制元件,为构建温敏复制载体奠定基础。
Actinobacillus pleuropneumoniae(APP),a member of the Pasteurellaceae family,is the causative agent of porcine contagious pleuropneumonia(PCP),which is worldwide epidemic and difficult to eradicate,and is responsible for substantial economic losses in the pig industry worldwide.Therefore,it is essential to prevent,control and treat this disease,but due to at least 15 distinct serotpyes and lack of cross-protection among them, this disease is dfficult to prevent and control.Moreover,the widespread use of antimicrobial agents to treat or prevent PCP,which force many pathogenic bacteria to become multidrug resistant bacteria,including APP.So it is more difficult to prevent and treat animal diseases.At present,in order to prevent and treat APP,we need to understand some knowledge about virulence factors,virulence associated factors,membrance proteins and flagellas in the level of molecular biology.However,the prerequisite condition of research on these genes is to possess some genetic operation tools,such as shuttle vector or high-efficency technology of constructing mutant.This study mainly focused on genetic operation tool,including two parts as below:
Isolation,sequencing and genetic characterization of A.pleuropneumoniae native plasmid pHB0503.Plasmid pHB0503 was extracted from Actinobacillus pleuropneumoniae HB0503,which was isolated in 2005.The complete 15.079 kb sequence of this plasmid,containing 16 ORFs,seven of which were associated with antibiotic resistance genes(sul2 catA3,aacC2,strA,strB',bla_(ROB-1) and aph(3)-I),was analyzed with regard to the organization and evolution.The experiment data indicated that pHB0503 arose through inter-plasmid recombination processes among other plasmids. In addition,co-transcription of the cluster of resistance genes from the promoter upstream of sul2 and bla_(ROB-1) was confirmed by RT-PCR.Then,the analysis of Rep protein may help us to construct stable shuttle vector or genetic tools,which is very useful for molecular biology research on APP.Moreover,the detection of antibiotic resistance genes could instruct the clinical use of antibiotic.
Construction of temperature-sensitive plasmids for A.pleuropneumoniae.PCR targeting system is a high-efficiency genetic modification system and has been widely used in research fields of microbiology.This system consists of four parts:recombinase systems,templates for PCR amplification of resistance gene,induced promoter and temperature- sensitive(TS) vector.At present,we already have possessed three parts.So the only element that we lack is TS vector.In order to construct a TS vector for APP,this study researched on a base of APP-E.coli shuttle vectors(pJN105 and pR318) and used two different kinds of methods(low-Fi PCR amplification method and the method involved in cloning genes into XL1-RED competence cell,which is deficient in primary DNA repair pathways) to construct it,which provided some supports to the further construction or research on TS vector.
引文
1.白淑民.猪传染性胸膜肺炎病的防治研究进展.甘肃畜牧兽医,1999,5:30-33
2.蔡宝祥.猪传染性胸膜肺炎的诊断与防治.辽宁畜牧兽医,1996,3:41-42
3.陈焕春主编.规模化猪场疫病控制与净化.北京:中国农业出版社,2000,273-276
4.陈华美,肖国生,文心田.猪胸膜肺炎放线杆菌的血清型分型及毒力因子研究进展.中国兽药杂志,2006,40:35-40
5.陈晓穗,汪保安,王琰.错配PCR致突变的实验条件研究.第二军医大学学报,2003,24:307-310
6.陈小玲,杨旭夫,朱士盛.猪传染性胸膜肺炎的流行现状和防制措施.中国兽医杂志,2001,37:33-35
7.葛堂栋,冯尔玲,晏本菊,王恒晖.黄留玉!痢疾杆菌酸抗性系统相关基因缺失突变体的构建生物技术通讯,2005,6:488-491
8.葛行义.胸膜肺炎放线杆菌TbpB-ELISA的建立及zmp和arcA/arcB基因的初步研究.[硕士学位论文].武汉:华中农业大学图书馆,2008:
9.何启盖,吴斌,吴信明,李英明,沈悦.猪接触传染性胸膜肺炎的防制现状.华中农业大学学报,2000,33:58-62
10.胡堃 史兆兴 王恒棵 冯尔玲 黄留玉Red重组系统在痢疾杆菌基因敲除中的应用研究.微生物学报,2003,43:740-746
11.李良军.胸膜肺炎放线杆菌JL03株的全基因组测序与flp操纵子的结构分析.[硕士学位论文].武汉:华中农业大学图书馆,2008
12.刘慧芳.胸膜肺炎放线杆菌质粒的序列浏定与分析.[硕士学位论文].杭州:浙江大学图书馆,2006
13.刘军发.胸膜肺炎放线杆菌PCR定向突变系统的初步建立及胸膜肺炎放线杆菌Om1A-ELISA检测方法的建立.[博士学位论文].武汉:华中农业大学图书馆,2005
14.逯忠新,鲁炳义.用间接血凝试验检测猪传染性胸膜肺炎.中国兽医科技,1999,29:25-27
15.逯忠新,赵萍,柳纪省,李宝玉.猪传染性胸膜肺炎的流行和防制.中国兽医杂志,2002,38:28
16.商霖,周锐,陈焕春,李薇,李良军,黎璐,张四化,李婷婷,李耀坤,刘磊,郭志伟,胸膜肺炎放线杆菌萘啶酸抗性菌株的选育和信号标签突变株的构建.微生物学报,2008,48:73-79
17.斯特劳[美],阿莱尔[加],蒙加林[美],泰勒[英]主编;赵德明,张中秋,沈建中主译.猪病学(第八版).北京:中国农业大学出版社,2000,357-367
18.王贵平,何启盖,刘军发,刘正飞,吴斌,陈焕春,石勇,冷光敏.猪伪狂犬 病和传染性胸膜肺炎混合感染.河北畜牧兽医,2004,20:33-34
19.吴硕显.胸膜肺炎放线杆菌血清型的地理分布.中国兽医杂志,1995,21:13
20.杨旭夫,彭发泉.胸膜肺炎嗜血杆菌的分离和鉴定.中国畜禽传染病,1990,4:1-3.
21.张剑,刘顺猛,班亚臣,王彦波,张国江,邵海宁,王彦军.猪传染性胸膜肺炎与猪丹毒混合感染.河北畜牧兽医,2004,20:36
22.张冬梅 肠致病性大肠杆菌致病机制的研究进展 国外医学流行病学传染病学分册.2001,01:27-30
23.张彦明,张耀相,刘春花,李健强.胸膜肺炎放线杆菌的分离鉴定及免疫预防.中国兽医科技,2002,32:21-22
24.赵书春等,周秀芬:邓子新大线性质pHZ1000,pHZ1001在链霉菌种间的接合转移.微生物学报,2000,40:235-239
25.周俊初,微生物遗传学.北京:中国农业出版社,2005:101-104
26.Anderson C,Potter A A,Gerlach G F.Isolation and molecular characterization of spontaneously occurring cytolysin-negative mutants of Actinobacillus pleuropneumoniae serotype 7.Infect Immun,1991,59:4110-4116
27.Auger E,Deslandes V,Ramjeet M,Contreras I,Nash JH,Harel J,Gottschalk M,Olivier M,Jacques M.Host-pathogen interactions of Actinobacillus pleuropneumoniae with porcine lung and tracheal epithelial cells.Infect Immun,2009,77:1426-1441.
28.Baltes N,Hennig-Pauka I,Gedach G F.Both transferfin binding proteins are virulence factors in Actinobacillus pleuropneumoniae serotype 7 infection.FEMS Microbiol Lett,2002,209:283-287
29.Baltes N,Tonpitak W,Hennig-Pauka I,Gruber A D,Gedach G F.Actinobacillus pleuropneumoniae serotype 7 siderophore receptor FhuA is not required for virulence.FEMS Microbiol Lett,2003,220:41-48
30.Baudin A.,.Ozier-Kalogeropoulos,A.Denouel.A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae.Nucleic Acids Research,1993,21:3329-3330
31.Bei W,He Q,Yan L,Fang L,Tan Y,Xiao S,Zhou R,Jin M,Guo A,LV J,Huang H,Chen H.Construction and characterization of a live,attenuated apxⅡCA inactivation mutant of Actinobacillus pleuropneumoniae lacking a drug resistance marker.FEMS Microbiol Lett,2005,243:21-27
32.Bertram T A.Actinobacillus pleuropneumoniae:molecular aspects of virulence and pulmonary injury.Can J Vet Res,1990,54:53-56
33.Blackall P J,Klaasen H L,van den Bosch H,Kuhnert P,Frey J.Proposal of a new serovar of Actinobacillus pleuropneumoniae:serovar 15.Vet Microbiol,2002,84:47-52
34.Blanco M,Gutierrez-Martin C B,Rodriguez-Ferri E F,Roberts M C,Navas J. Distribution of tetracycline resistance genes in Actinobacillus pleuropneumoniae isolates from Spain.Antimicrob Agents Chemother,2006,50:702-708
35.Blanco M,Kadlec K,Gutierrez Martin C B,de la Fuente A J,Schwarz S,Navas J.Nucleotide sequence and transfer properties of two novel types of Actinobacillus pleuropneumoniae plasmids carrying the tetracycline resistance gene tet(H).J Antimicrob Chemother,2007,60:864-867
36.Boros I,Posfai G,Venetianer P High-copy-number derivatives of the plasmid cloning vector pBR322.Gene,1984,30:257-260
37.Bosse J T,Janson H,Sheehan B J,Beddek A J,Rycroft A N,Kroll J S,Langford P R.Actinobacillus pleuropneumoniae:pathobiology and pathogenesis of infection.Microbes Infect,2002,4:225-235
38.Bosse J T,MacInnes J I.Urease activity may contribute to the ability of Actinobacillus pleuropneumoniae to establish infection.Can J Vet Res,2000,64:145-150
39.Bosse J T,Nash J H,Kroll J S,Langford P R.Harnessing natural transformation in Actinobacillus pleuropneumoniae:a simple method for allelic replacements.FEMS Microbiol Lett,2004,233:277-281
40.Braun V.Iron uptake mechanisms and their regulation in pathogenic bacteria.Int J Med Microbiol,2001,291:67-79.
41.Briggs R E,Tatum F M.Generation and molecular characterization of new temperature-sensitive plasmids intended for genetic engineering of Pasteurellaceae.Appl Environ Microbiol,2005,71:7187-7195
42.Bunka S,Christensen C,Potter A A,Willson P J,Gerlach G F.Cloning and characterization of a protective outer membrane lipoprotein of Actinobacillus pleuropneumoniae serotype 5.Infect Immun,1995,63:2797-2800
43.Byrd W.Hooke A M.Temperature-sensitive mutants of Actinobacillus pleuropneumoniae induce protection in mice.Infect Immun,1997,65:2206-2210
44.Chai L L,Dave S W O,Steve K W O.Quantitative real-time polymerase chain reaction for determination of plasmid copy number in bacteria.Journal of Microbiological Method,2006,65:258-267
45.Chang C F,Yeh T M,Chou C C,Chang Y F,Chiang T S.Antimicrobial susceptibility and plasmid analysis of Actinobacillus pleuropneumoniae isolated in Taiwan.Vet Microbiol,2002,84:169-177
46.Chang Y F,Shi J,Shin S J,Lein D H.Sequence analysis of the ROB-1beta-lactamase gene from Actinobacillus pleuropneumoniae.Vet Microbiol,1992,32:319-325
47.Chen C Y,Nace G W,Solow B,Fratomico P.Complete nucleotide sequences of 84.5- and 3.2-kb plasmids in the multi-antibiotic resistant Salmonella enterica serovar Typhimurium U302 strain G8430,Plasmid,2007,57:29-43
48.Chen Y T,Shu H Y,Li L H,Liao T L,Wu K M,Shiau Y R,Su I J,Yan J J Tsai S F, Lauderdale T L.Complete nucleotide sequence of pK245,a 98-kilobase plasmid conferring quinolone resistance and extended-spectrum- beta- lactamase activity in a clinical Klebsiella pneumoniae isolate.Antimicrob Agents Chemother,2006,50:3861-3866.
49.Coppella S J,Acheson C M,Dhurjati P.Measurement of copy number using HPLC.Biotechnol Bioeng,1987,29:646-647
50.Datsenko K A,Wanner B L.One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.Proc Natl Acad Sci,2000,97:6640-6645
51.Deslandes V,Nash J H,Harel J,Coulton J W,Jacques M.Transcriptional profiling of Actinobacillus pleuropneumoniae under iron-restricted conditions.BMC Genomics,2007,13:68-72.
52.del Solar G,Giraldo R,Ruiz-Echevarria M J,Espinosa M,Diaz-Orejas.Replication and control of circular bacterial plasmids.Microbiol Mol Biol Rev,1998,62:434-464
53.Dixon LG,Albritton WL,Willson PJ.An analysis of the complete nucleotide sequence of the Haemophilus ducreyi broad-host-range plasmid pLS88.Plasmid,1994,32:228-232.
54.Dom P,Hommez J,Castryck F,Devriese L A,Haesebrouck F.Serotyping and quantitative determination of in vitro antibiotic susceptibility of Actinobacillus pleuropneumoniae strains isolated in Belgium(July 1991-August 1992).Vet Q,1994,16:10-13
55.Dreyfus A,Schaller A,Nivollet S,Segers R P,Kobisch M,Mieli L,Soerensen V,Hussy D,Miserez R,Zimmermann W,Inderbitzin F,Frey J.Use of recombinant ApxⅣ in serodiagnosis of Actinobacillus pleuropneumoniae infections,development and prevalidation of the ApxⅣ ELISA.Vet Microbiol,2004,99:227-238
56.Dubreuil J D,Jacques M,Mittal K R,Gottschalk M.Actinobacillus pleuropneumoniae surface polysaccharides:their role in diagnosis and immunogenicity.Anim Health Res Rev,2000,1:73-93
57.Fenwick B W,Osburn B I.Immune responses to the lipopolysaccharides and capsular polysaccharides of Haemophilus pleuropneumoniae in convalescent and immunized pigs.Infect Immun,1986,54:575-582
58.Fenwick B W,Osburn B I,Olander H J.Isolation and biological characterization of two lipopolysaccharides and a capsular-enriched polysaccharide preparation from Haemophilus pleuropneumoniae.Am J Vet Res,1986,47:1433-1441
59.Frey J.Virulence in Actinobacillus pleuropneumoniae and RTX toxins.Trends Microbiol,1995,3:257-261
60.Frey J,Bosse J T,Chang Y F,Cullen J M,Fenwick B,Gerlach G F,Gygi D,Haesebrouck F,Inzana T J,Jansen R.Actinobacillus pleuropneumoniae RTX-toxins:uniform designation of haemolysins,cytolysins,pleurotoxin and their genes.J Gen Microbiol,1993,139:1723-1728
61.Frey J,Kuhnert P,Villiger L,Nicolet J.Cloning and characterization of an Actinobacillus pleuropneumoniae outer membrane protein belonging to the family of PAL lipoproteins.Res Microbiol,1996,147:351-361
62.Frey J,Nicolet J.Hemolysin patterns of Actinobacillus pleuropneumoniae.J Clin MicrobioI,1990,28:232-236
63.Frey J,Nicolet J.Regulation of hemolysin expression in Actinobacillus pleuropneumoniae serotype 1 by Ca~(2+).Infect Immun,1988,56:2570-2575
64.Fuller C A,Yu R,Irwin S W,Schryvers A B.Biochemical evidence for a conserved interaction between bacterial transferrin binding protein A and transferrin binding protein B.Microb Pathog,1998,24:75-87
65.Fuller T E,Thacker B J,Duran C O,Mulks M H.A genetically-defined riboflavin auxotroph of Actinobacillus pleuropneumoniae as a live attenuated vaccine.Vaccine,2000,18:2867-2877
66.Gerami-Nejad M,Berman J,Gale C A.Cassettes for PCR-mediated construction of green,yellow,and cyan fluorescent protein fusions in Candida atbicans.Yeast,2001,18:859-864
67.Gerlach G F,Anderson C,Klashinsky S,Rossi-Campos A,Potter A A,Willson P J.Molecular characterization of a protective outer membrane lipoprotein(OmlA) from Actinobacillus pleuropneumoniae serotype 1.Infect Immun,1993,61:565-572
68.Gerlach G F,Klashinsky S,Anderson C,Potter A A,Willson P J.Characterization of two genes encoding distinct transferrin-binding proteins in different Actinobacillus pleuropneumoniae isolates.Infect Immun,1992,60:3253-3261
69.Gilbride K A,Rosendal S,Brunton J L.Plasmid mediated antimicrobial resistance in Ontario isolates of Actinobacillus(Haemophilus) pleuropneumoniae.Can J Vet Res.1989.53:38-42
70.Gonzalez G C,Caamano D L,Schryvers A B.Identification and characterization of a porcine-specific transferrin receptor in Actinobacillus pleuropneumoniae.Mol Microbiol,1990,4:1173-1179
71.Gonzalez G C,Yu R H,Rosteck P R,Jr.,Schryvers A B.Sequence,genetic analysis,and expression of Actinobacillus pleuropneumoniae transferrin receptor genes.Microbiology,1995,141:2405-2416
72.Gutierrez C B,Rodriguez Barbosa J I,Gonzalez O R,Tascon R I,Rodriguez Ferri E F.Viability of Actinobacillus pleuropneumoniae in frozen pig lung samples and comparison of different methods of direct diagnosis in fresh samples.Comp Immunol Microbiol Infect Dis,1992,15:89-95
73.Gutierrez C B,Rodriguez Barbosa J I,Tascon R I,Costa L,Riera P,Rodriguez Ferri E F.Serological characterisation and antimicrobial susceptibility of Actinobacillus pleuropneumoniae strains isolated from pigs in Spain.Vet Rec,1995,137:62-64
74.Habrun B,Bilic V,Humski A.Comparison of ELISA and 2-META assays used in serological diagnosis of infection with Actinobacillus pleuropneumoniae serotypes 2 and 4-7 in breeding pigs in Croatia.Prey Vet Med,1998b,36:179-186
75.Habrun B,Frey J,Bilic V,Nicolet J,Humski A.Prevalence of serotypes and toxin types of Actinobacillus pleuropneumoniae in pigs in Croatia.Vet Rec,1998a,143:255-256
76.Haesebrouck F,Chiers K,Van Overbeke I,Ducatelle R.Actinobacillus pleuropneumoniae infections in pigs:the role of virulence factors in pathogenesis and protection.Vet Microbiol,1997,58:239-249
77.Hamer-Barrera R,Godinez D,Enriquez VI,Vaca-Pacheco S,Martinez-Zunga R,Talamas-Rohana P,Suarez-G(u|¨)emez F,de la Garza M.Adherence of Actinobacillus pleuropneumoniae serptype 1 to swine buccal epithelial cell involves fibronectin.Can J Vet Res,2004,68:33-41
78.Hields M S,Reagin M J,Gerger R R.TOM new acrometic degradative plasmid from Burkholdena(Pseudomous) cepacia G4.Appl environ Microbiol,1995,61:1352-1356
79.Hinnebusch J,Barbour A G.Linear- and circular-plasmid copy numbers in Borrelia burgdorferi.J Bacteriol.1992,174:5251-5257.
80.Hirsh,D.C.,Martin,L.D.,Libal,M.C.Plasmid-mediated antimicrobial resistance in Haemophilus pleuropneumoniae.Am.J.Vet.Res,1982,43:269-272.
81.Huang H,Potter A A,Campos M,Leighton F A,Willson P J,Haines D M,Yates W D.Pathogenesis of porcine Actinobacillus pleuropneumonia,part Ⅱ:roles of proinflammatory cytokines.Can J Vet Res,1999,63:69-78
82.Husseiny M I,Hensel M.Evaluation of an intracellular-activated promoter for the generation of live Salmonella recombinant vaccines.Vaccine,2005,23:2580-2590.
83.Inzana T J.Capsules and virulence in the HAP group of bacteria.Can J Vet Res,1990,54:22-27
84.Inzana T J.Simplified procedure for preparation of sensitized latex particles to detect capsular polysaccharides:application to typing and diagnosis of Actinobacillus pleuropneumoniae.J Clin Microbiol,1995,33:2297-2303
85.Inzana T J,Ma J,Workman T,Gogolewski R P,Anderson P.Virulence properties and protective efficacy of the capsular polymer of Haemophilus(Actinobacillus)pleuropneumoniae serotype 5.lnfect Immun,1988,56:1880-1889
86.Inzana T J,Mathison B.Serotype specificity and immunogenicity of the capsular polymer of Haemophilus pleuropneumoniae serotype 5.Infect Immun,1987,55:1580-1587
87.Inzana T J,Todd J,Veit H P.Safety,stability,and efficacy of noncapsulated mutants of Actinobacillus pleuropneumoniae for use in live vaccines.Infect Immun,1993,61:1682-1686
88.Ishii H,Fukuyasu T,Iyobe S,Hashimoto H.Characterization of newly isolated plasmids from Actinobacillus pleuropneumoniae.Am J Vet Res,1993,54:701-708.
89.Ishii H,Hayashi F,Iyobe S,Hashimoto H.Characterization and classification of Actinobacillus(Haemophilus) pleuropneumoniae plasmids.Am J Vet Res.,1991,52:1816-1820.
90.Ishii H,Nakasone Y,Shigehara S,Honma K,Araki Y,Iyobe S,Hashimoto H.Drug-susceptibility and isolation of a plasmid in Haemophilus(Actinobacillus)pleuropneumoniae.Nippon Juigaku Zasshi,1990,52:1-9.
91.Ito H,Ishii H,Akiba M.Analysis of the complete nucleotide sequence of an Actinobacillus pleuropneumoniae streptomycin-sulfonamide resistance plasmid,pMS260.Plasmid,2004,51:41-47
92.Ito H,Uchida I,Sekizaki T,Ooishi E,Kawai T,Okabe T,Taneno A,Terakado N.Molecular cloning of an Actinobacillus pleuropneumoniae outer membrane lipoprotein(OmlA) from serotype 5a.Microb Pathog,1995,18:29-36
93.Jensen A E,Bertram T A.Morphological and biochemical comparison of virulent and avirulent isolates of Haemophilus pleuropneumoniae serotype 5.Infect Immun,1986,51:419-424
94.Jolie R A,Mulks M H,Thacker B J.Cross-protection experiments in pigs vaccinated with Actinobacillus pleuropneumoniae subtypes 1A and 1B.Vet.Microbiol,1995,45:383-391
95.Juteau J M,Sirois M,Medeiros A A,Levesque R C.Molecular distribution of ROB-1 beta-lactamase in Actinobacillus pleuropneumoniae.Antimicrob Agents Chemother,1991,35:1397-402.
96.Kamp E M,Popma J K,Anakotta J,Smits M A.Identification of hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae by use of monoclonal antibodies.Infect Immun,1991,59:3079-3085
97.Kamp E M,Popma J K,Van Leengoed L A.Serotyping of Haemophilus pleuropneumoniae in the Netherlands:with emphasis on heterogeneity within serotype 1 and(proposed) serotype 9.Vet Microbiol,1987,13:249-257
98.Kamp E M,Vermeulen T M,Smits M A,Haagsma J.Production of Apx toxins by field strains of Actinobacillus pleuropneumoniae and Actinobacillus suis.Infect Immun,1994,62:4063-4065
99.Kang M,Zhou R,Liu L,Langford P R,Chen H.Analysis of an Actinobacillus pleuropneumoniae multi-resistance plasmid,pHB0503.Plasmid,2009,61:135-139.
100.Karl Friehs.Plasmid Copy Number and Plasmid Stability.Adv Biochem Engin/Biotechnol,2004,86:47-82
101.Kawahara K,Kawase H,Nakai T,Kume K,Danbara H.Drug resistance plasmids of Actinobacillus(Haemophilus)pleuropneumoniae serotype 2 strains isolated from swine.Kitasato Arch Exp Med,1990,63:131-136.
102.Kehrenberg C,Meunier D,Targant H,Cloeckaert A,Schwarz S,Madec J Y.Plasmid-mediated florfenicol resistance in Pasteurella trehalosi.J Antimicrob Chemother,2006,58:13-17.
103.Kehrenberg C,Schulze-Tanzil G,Martel J L,Chashu-Dancla E,Schwarz S. Antimicrobial resistance in Pasteurella and Mannheimia:epidemiology and genetic basis.Vet.Res,2001,32:323-339.
104.Kehrenberg C,Schwarz S.Nucleotide sequence and organization of plasmid pMVSCS1 from Mannheimia varigena:identification of a multiresistance gene cluster.J.Antimicrob.Chemother,2002;49:383-386.
105.Kilian M,Nicolet J,and Biberstein E L.Biochemical and serological characterization of Haemophilus pleuropneumoniae(Matthews and Pattison,1961)Shope 1964 and proposal ofa neotype strain.Int.d.Syst.Bacteriol,1978;28:20-26.
106.Kiuchi A,Hara M,Tabuchi K.Drug resistant plasmid of Actinobacillus pleuropneumoniae isolated from swine pleuropneumonia in Thailand.Kansenshogaku Zasshi,1992,66:1243-1247.
107.Kraig E,Dailey T,Kolodrubetz D.Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans:homology to the alpha-hemolysin/leukotoxin gene family.Infect Immun,1990,58:920-929
108.Levonen K,Seppanen J,Veijalainen P.Antibodies against 12 serotypes of Actinobacillus pleuropneumoniae in finnish slaughter sows.Zentralbl Veterinarmed B,1996,43:489-495
109.Lin L,Bei W,Sha Y,Liu J,Guo Y,Liu W,Tu S,He Q,Chen H.Construction and immunogencity of a DeltaapxⅠC/DeltaapxⅡC double mutant of Actinobacillus pleuropneumoniae serovar 1.FEMS Microbiol Lett,2007,274:55-62
110.Li L,Zhou R,Li T,Kang M,Wan Y,Xu Z,Chen H.Enhanced biofilm formation and reduced virulence of Actinobacillus pleuropneumoniae luxS mutant.Microb Pathog.2008,45:192-200
111.Liu J,Chen X,Tan C,Guo Y,Chen Y,Fu S,Bei W,Chen H.Invivo induced RTX toxin ApxⅣA is essential for the full virulence of Actinobacillus pleuropneumoniae.Vet Microbiol.2009.[Epub ahead of print]
112.Livrelli V,Peduzzi J,Joly B.Sequence and molecular characterization of the ROB-1b-lactamase gene from Pasteurella haemolytica.Antimicrob Agents Chemother,1991,35:242-251.
113.Maas A,Jacobsen I D,Meens J,Gerlach G F.Use of an Actinobacillus pleuropneumoniae multiple mutant as a vaccine that allows differentiation of vaccinated and infected animals.Infect Immun,2006,74:4124-4132
114.Martin P R,Mulks M H.Cloning and characterization of a gene encoding an antigenic membrane protein from Actinobacillus pleuropneumoniae with homology to ABC transporters.FEMS Immunol Med Microbiol,1999,25:245-254
115.Matter D,Rossano A,Sieber S,Perreten V.Small multidrug resistance plasmids in Actinobacillus porcitonsillarum,Plasmid 2008,59:144-152
116.Mattick J S.Type Ⅳ pili and twitching motility.Annu Rev Microbiol,2002,56:289-314
117.Maudsley J R,Kadis S,Mayberry W R.Isolation,purification,and partial characterization of a lipopolysaccharide from Haemophilus pleuropneumoniae. Infect Immun, 1986, 51: 501-506
118. Mayer M P A new set of useful cloning and expression vectors derived from pBlueScript. Gene, 1995 ,163: 41-46
119. Mikael L G, Pawelek P D, Labrie J, Sirois M, Coulton J W, Jacques M. Molecular cloning and characterization of the ferric hydroxamate uptake (fhu) operon in Actinobacillus pleuropneumoniae. Microbiology, 2002,148: 2869-2882.
120. Mikael L G, Srikumar R, Coulton J W, Jacques M. fhuA of Actinobacillus pleuropneumoniae encodes a ferrichrome receptor but is not regulated by iron. Infect Immun, 2003, 71: 2911-2915.
121. Miller C A, Cohen S N. The partition (par) locus of pSC101 is an enhancer of plasmid incompatibility. Mol Microbiol, 1993, 9: 695-702
122. Min K, Chae C. Serotype and apx genotype profiles of Actinobacillus pleuropneumoniae field isolates in Korea. Vet Rec, 1999, 145: 251-254
123. Mittal K R, Higgins R, Lariviere S, Nadeau M. Serological characterization of Actinobacillus pleuropneumoniae strains isolated from pigs in Quebec. Vet Microbiol, 1992, 32: 135-148
124. Mulks M H, Moxon E R, Bricker J, Wright A, Plaut A G. Examination of Haemophilus pleuropneumoniae for immunoglobulin A protease activity. Infect Immun, 1984,45: 276-277
125. Murphy K C. Use of bacteriophage lambda recombination functions to promote gene replacement in Escherichia coli. J Bacteriol, 1998, 180: 2063-2071.
126. Murray I A, Hawkins A R, Keyte J W, Shaw W V. Nucleotide sequence analysis and overexpression of the gene encoding a type III chloramphenicol acetyltransferase. Biochem J, 1988,252: 173-179.
127. Muyrers J P, Zhang Y, Testa G, Stewart A F. Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Res, 1999, 27: 1555-1557.
128. Negrete-Abascal E, Reyes M E, Garcia R M, Vaca S, Giron J A, Garcia O, Zenteno E, De La Garza M. Flagella and Motility in Actinobacillus pleuropneumoniae. J Bacteriol, 2003, 185: 664-668
129. Negrete-Abascal E, Tenorio V R, Guerrero A L, Garcia R M, Reyes M E, de la Garza M. Purification and characterization of a protease from Actinobacillus pleuropneumoniae serotype 1, an antigen common to all the serotypes. Can J Vet Res, 1998,62:183-190
130. Negrete-Abascal E, Tenorio V R, Serrano J J, Garcia C, de la Garza M. Secreted proteases from Actinobacillus pleuropneumoniae serotype 1 degrade porcine gelatin, hemoglobin and immunoglobulin A. Can J Vet Res, 1994, 58: 83-86
131. Nielsen R. Haemophilus pleuropneumoniae serotypes-cross protection experiments. Nord Vet Med, 1984, 36: 221-234
132. Nielsen R, Andresen L O, Plambeck T, Nielsen J P, Krarup L T, Jorsal S E. Serological characterization of Actinobacillus pleuropneumoniae biotype 2 strains isolated from pigs in two Danish herds. Vet Microbiol, 1997, 54: 35-46
133. Nina B, Walaiporn T, Gerlald F.G, et al. Actinobacillus pleuropneumoniae iron transport and crease activity:effects on bacterial virulence and host immune response. Infect.Immun, 2001, 69: 472-478.
134. Novick R P. Plasmid incompatibility. Microbiol Rev. 1987; 51: 381-395
135. Oswald W, Tonpitak W, Ohrt G, Gerlach G. A single-step transconjugation system for the introduction of unmarked deletions into Actinobacillus pleuropneumoniae serotype 7 using a sucrose sensitivity marker. FEMS Microbiol Lett, 1999, 179: 153-160
136. Paulsson J, Ehrenberg M. Molecular clocks reduce plasmid loss rates: the R1 case. J Mol Biol, 2000, 297: 179-192
137. Pagotto F, Dillon JAMultiple origins and replication proteins influence biological properties of beta-lactamase-producing plasmids from Neisseria gonorrhoeae. J Bacteriol. 2001, 183: 5472-5481.
138. Pawelek P D, Coulton J W. Hemoglobin-binding protein HgbA in the outer membrane of Actinobacillus pleuropneumoniae: homology modelling reveals regions of potential interactions with hemoglobin and heme. J Mol Graph Model, 2004,23:211-221
139. Perry M B. Structural analysis of the lipopolysaccharide of Actinobacillus (Haemophilus) pleuropneumoniae serotype 10. Biochem Cell Biol, 1990, 68:808-810
140. Poteete A R, Fenton A C, Murphy K C. Roles of RuvC and RecG in phage lambda red-mediated recombination. J Bacteriol, 1999,181: 5402-5408.
141. Power S B, Quigley F C, Pritchard D G, Croston P. Porcine pleuropneumonia associated with Haemophilus pleuropneumoniae serotype 3 in the Republic of Ireland. Vet Rec, 1983, 113: 113-114
142. Projan S J, Carleton S, Novick R P. Determination of plasmid copy number by fluorescence densitometry. Plasmid, 1983, 9: 182-190
143. Pushnova E A , Geier M , Zhu Y S. An easy and accurate agarose gelassay for quantitation of bacterial plasmid copy numbers. Anal Biochem, 2000, 284: 70—76.
144. Rather P N, Mann P A, Mierzwa R Miller G H, Shaw K J. Analysis of the aac(3)-VIa gene encoding a novel 3-N-acetyltransferase. Antimicrob Agents Chemother, 1993, 37: 2074-2079
145. Redfield R J, Findlay W A, Bosse J, Kroll J S, Cameron A D, Nash J H. Evolution of competence and DNA uptake specificity in the Pasteurellaceae. BMC Evol Biol, 2006, 6: 82
146. Rioux S, Begin C, Dubreuil J D, Jacques M. Isolation and characterization of LPS mutants of Actinobacillus pleuropneumoniae serotype 1. Curr Microbiol, 1997, 35: 139-144
147. Rioux S, Galarneau C, Harel J, Frey J, Nicolet J, Kobisch M, Dubreuil J D, Jacques M. Isolation and characterization of mini-Tn10 lipopolysaccharide mutants of Actinobacillus pleuropneumoniae serotype 1. Can J Microbiol, 1999,45: 1017-1026
148. Rioux S, Galarneau C, Harel J, Kobisch M, Frey J, Gottschalk M, Jacques M. Isolation and characterization of a capsule-deficient mutant of Actinobacillus pleuropneumoniae serotype 1. Microb Pathog, 2000,28: 279-289
149. Sambrook J, Russell D W. Molecular cloning: a laboratory manual (Third Edition). New York: Cold Spring Harbor Press, 2001.
150. San Millan A, Escudero J A., Catalan A, Nieto S, Farelo F, Gibert M, Moreno M A, Domingnesc L. P-lactam resistance in Haemophilus parasuis is mediated by plasmid pB1000 bearing blaROB-1. Antimicrob. Agents Chemother 2007; 51: 2260- 2264
151. Satran P, Nedbalcova K. Prevalence of serotypes, production of Apx toxins, and antibiotic resistance in strains of Actinobacillus pleuropneumoniae isolated in the Czech Republic. Vet Med, 2002,47: 92-98
152. Schaller A, Djordjevic SP, Eamens GJ, Forbes W A, Kuhu R, Gonzale-zorn B, Kuhnerto P, Gottschalk M, Nicolet J. Identification and detection of Actinobacillus pleuropneumoniae by PCR based on the gene apxIVA. Vet Microbiol., 2001, 79: 47-62.
153. Scholz P, Haring V, Wittmann-Liebold B, Ashman K, Bagdasarin M, Scherzinger E, Frey J. Complete nucleotide sequence and gene organization of the broad-host-range plasmid RSF1010. Gene, 1989, 75: 271-88.
154. Shakarji L, Mikael L G, Srikumar R, Kobisch M, Coulton J W, Jacques M. Fhua and HgbA, outer membrane proteins of Actinobacillus pleuropneumoniae: their role as virulence determinants. Can J Microbiol, 2006, 52: 391-396
155. Sheehan B J, Bosse J T, Beddek A J, Rycroft A N, Kroll J S, Langford P R. Identification of Actinobacillus pleuropneumoniae genes important for survival during infection in its natural host. Infect Immun, 2003, 71: 3960-3970
156. Srikumar R, Mikael L G, Pawelek P D, Khamessan A, Gibbs B F, Jacques M, Coulton J W. Molecular cloning of haemoglobin-binding protein HgbA in the outer membrane of Actinobacillus pleuropneumoniae. Microbiology, 2004, 150: 1723-1734
157. Strathdee C A, Lo R Y. Cloning, nucleotide sequence, and characterization of genes encoding the secretion function of the Pasteurella haemolytica leukotoxin determinant. J Bacteriol, 1989, 171: 916-928
158. Susan E.H.West, Mary Jo M. Construction of Actinobacillus pleuropneumoniae-Escherichia coli cosmid cloning vector. Gene, 1995, 160:87-88
159. Susan E.H.West, Mary Jo M.Romero, Laura B.Regassa, Nicolette .A. Construction of Actinobacillus pleuropneumoniae-Escherichia coli shuttle vector:expression of antibiotic-resistance genes. Gene, 1995, 160: 81-86
160. Tadjine M, Mittal K R. Study of antigenic heterogeneity among Actinobacillus pleuropneumoniae serotype 7 strains.Vet Microbiol,2001,78:49-60
161.Takamatsu D,Osaki M,Sekizaki T.Thermosensitive suicide vectors for gene replacement in Streptococcus suis.Plasmid,2001,46:140-148
162.Tang J,Zhou R,Shi X,Kang M,Wang H,Chen H.Two thermostable nucleases coexisted in Staphylococcus aureus:evidence from mutagenesis and in vitro expression.FEMS Microbiol Lett,2008,284:176-183
163.Tascon Cabrero R I,Vazquez-Boland J A,Gutierrez C B,Rodriguez-Barbosa J I,Rodriguez-Ferri E F.Actinobacillus pleuropneumoniae does not require urease activity to produce acute swine pleuropneumonia.FEMS Microbiol Lett,1997,148:53-57
164.Tascon R I,Rodriguez-Ferri E F,Gutierrez-Martin C B,Rodriguez-Barbosa I,Berche P,Vazquez-Boland J A.Transposon mutagenesis in Actinobacillus pleuropneumoniae with a Tn10 derivative.J Bacteriol,1993,175:5717-5722
165.Tascon R I,Vazquez-Boland J A,Gutierrez-Martin C B,Rodriguez-Barbosa I,Rodriguez-Ferri E F.The RTX haemolysins ApxⅠ and ApxⅡ are major virulence factors of the swine pathogen Actinobacillus pleuropneumoniae:evidence from mutational analysis.Mol Microbiol,1994,14:207-216
166.Tonpitak W,Baltes N,Hennig-Pauka I,Gerlach G F.Construction of an Actinobacillus pleuropneumoniae serotype 2 prototype live negative-marker vaccine.Infect Immun,2002,70:7120-7125
167.Tracy E,Ye F,Baker B D,Munson R S Jr.Construction of non-polar mutants in Haemophilus influenzae using FLP recombinase technology.BMC Mol Biol,2008,9:101
168.Turni C,Blackall P J.An evaluation of the apxⅣA based PCR-REA method for differentiation of Actinobacillus pleuropneumoniae.Vet Microbiol,2007,121:163-169
169.Udeze F A,Latimer K S,Kadis S.Role of Haemophilus pleuropneumoniae lipopolysaccharide endotoxin in the pathogenesis of porcine Haemophilus pleuropneumonia.Am J Vet Res,1987,48:768-773
170.U.N streips and R.E.Yasbin,Modem Microbial Genetics,Wileyliss Inc,1991
171.van den Bosch H,Frey J.Interference of outer membrane protein PalA with protective immunity against Actinobacillus pleuropneumoniae infections in vaccinated pigs.Vaccine,2003,21:3601-3607
172.Vigre H,Angen O,Barfod K,Lavritsen D T,Sorensen V.Transmission of Actinobacillus pleuropneumoniae in pigs under field-like conditions:emphasis on tonsillar colonisation and passively acquired colostral antibodies.Vet Microbiol,2002,89:151-159
173.Vliegenthart J S,Ketelaar-van Gaalen P A,van de Klundert J A.Nucleotide sequence of the aacC3 gene,a gentamicin resistance determinant encoding aminoglycoside-(3)-N-acetyltransferase Ⅲ expressed in Pseudomonas aeruginosa but not in Escherichia coli.Antimicrob Agents Chemother,1991,35:892-897
174.Ward A C,Hillier A J,Davidson B E,Powell I B.Stability analysis of the Lactococcus lactis DRC1 lactose plasmid using pulsed-field gel electrophoresis.Plasmid,1993,29:70-3.
175.Ward C K,Inzana T J.Resistance of Actinobacillus pleuropneumoniae to bactericidal antibody and complement is mediated by capsular polysaccharide and blocking antibody specific for lipopolysacchadde.J Immunol,1994,153:2110-2121
176.Wandersman C,Stojiljkovic I.Bacterial heme sources:the role of heme,hemoprotein receptors and hemophores.Curr Opin Microbiol,2000,3:215-220.
177.Welch R A.Pore-forming cytolysins of gram-negative bacteria.Mol Microbiol,1991,5:521-528
178.Willson P J,Deneer H G,Potter A,Albritton W.Characterization of a streptomycin-sulfonamide resistance plasmid from Actinobacillus pleuropneumoniae Antimicrob Agents Chemother,1989,33:235-238
179.Wright C L,Strugnell R A,Hodgson A L.Characterization of a Pasteurella multocida plasmid and its use to express recombinant proteins in P.multocida.Plasmid,1997,37:65-79.
180.Xu F,Chen X,Shi A,Yang B,Wang J,Li Y,Guo X,Blackall P J,Yang H.Characterization and immunogenicity of an apxⅠA mutant of Actinobacillus pleuropneumoniae.Vet Microbiol,2006,118:230-239
181.Xu Z,Zhou Y,Li L,Zhou R,Xiao S,Wan Y,Zhang S,Wang K,Li W,Li L,Jin H,Kang M,Dalai B,Li T,Liu L,Cheng Y,Zhang L,Xu T,Zheng H,Pu S,Wang B,Gu W,Zhang XL,Zhu GF,Wang S,Zhao GP,Chen H.Genome biology of Actinobacillus pleuropneumoniae JL03,an isolate of serotype 3 prevalent in China.PLoS ONE,2008,3:e1450.
182.Ying-Tsong Chen,Hung-Yu Shu,Ling-Hui Li,Tsai-Lien Liao,Keh-Ming Wu,Yih-Ru Shiau,4 Jing-Jou Yan,Ih-Jen Su,Shih-Feng Tsai,and Tsai-Ling Lauderdale..Complete Nucleotide Sequence of pK245,a 98-Kilobase Plasmid Conferring Quinolone Resistance and Extended-Spectnum-Lactamase Activity in a Clinical Klebsiella pneumoniae Isolate.Antimicrob Agents Chemother,2006,50:3861-3866,
2.蔡宝祥.猪传染性胸膜肺炎的诊断与防治.辽宁畜牧兽医,1996,3:41-42
3.陈焕春主编.规模化猪场疫病控制与净化.北京:中国农业出版社,2000,273-276
4.陈华美,肖国生,文心田.猪胸膜肺炎放线杆菌的血清型分型及毒力因子研究进展.中国兽药杂志,2006,40:35-40
5.陈晓穗,汪保安,王琰.错配PCR致突变的实验条件研究.第二军医大学学报,2003,24:307-310
6.陈小玲,杨旭夫,朱士盛.猪传染性胸膜肺炎的流行现状和防制措施.中国兽医杂志,2001,37:33-35
7.葛堂栋,冯尔玲,晏本菊,王恒晖.黄留玉!痢疾杆菌酸抗性系统相关基因缺失突变体的构建生物技术通讯,2005,6:488-491
8.葛行义.胸膜肺炎放线杆菌TbpB-ELISA的建立及zmp和arcA/arcB基因的初步研究.[硕士学位论文].武汉:华中农业大学图书馆,2008:
9.何启盖,吴斌,吴信明,李英明,沈悦.猪接触传染性胸膜肺炎的防制现状.华中农业大学学报,2000,33:58-62
10.胡堃 史兆兴 王恒棵 冯尔玲 黄留玉Red重组系统在痢疾杆菌基因敲除中的应用研究.微生物学报,2003,43:740-746
11.李良军.胸膜肺炎放线杆菌JL03株的全基因组测序与flp操纵子的结构分析.[硕士学位论文].武汉:华中农业大学图书馆,2008
12.刘慧芳.胸膜肺炎放线杆菌质粒的序列浏定与分析.[硕士学位论文].杭州:浙江大学图书馆,2006
13.刘军发.胸膜肺炎放线杆菌PCR定向突变系统的初步建立及胸膜肺炎放线杆菌Om1A-ELISA检测方法的建立.[博士学位论文].武汉:华中农业大学图书馆,2005
14.逯忠新,鲁炳义.用间接血凝试验检测猪传染性胸膜肺炎.中国兽医科技,1999,29:25-27
15.逯忠新,赵萍,柳纪省,李宝玉.猪传染性胸膜肺炎的流行和防制.中国兽医杂志,2002,38:28
16.商霖,周锐,陈焕春,李薇,李良军,黎璐,张四化,李婷婷,李耀坤,刘磊,郭志伟,胸膜肺炎放线杆菌萘啶酸抗性菌株的选育和信号标签突变株的构建.微生物学报,2008,48:73-79
17.斯特劳[美],阿莱尔[加],蒙加林[美],泰勒[英]主编;赵德明,张中秋,沈建中主译.猪病学(第八版).北京:中国农业大学出版社,2000,357-367
18.王贵平,何启盖,刘军发,刘正飞,吴斌,陈焕春,石勇,冷光敏.猪伪狂犬 病和传染性胸膜肺炎混合感染.河北畜牧兽医,2004,20:33-34
19.吴硕显.胸膜肺炎放线杆菌血清型的地理分布.中国兽医杂志,1995,21:13
20.杨旭夫,彭发泉.胸膜肺炎嗜血杆菌的分离和鉴定.中国畜禽传染病,1990,4:1-3.
21.张剑,刘顺猛,班亚臣,王彦波,张国江,邵海宁,王彦军.猪传染性胸膜肺炎与猪丹毒混合感染.河北畜牧兽医,2004,20:36
22.张冬梅 肠致病性大肠杆菌致病机制的研究进展 国外医学流行病学传染病学分册.2001,01:27-30
23.张彦明,张耀相,刘春花,李健强.胸膜肺炎放线杆菌的分离鉴定及免疫预防.中国兽医科技,2002,32:21-22
24.赵书春等,周秀芬:邓子新大线性质pHZ1000,pHZ1001在链霉菌种间的接合转移.微生物学报,2000,40:235-239
25.周俊初,微生物遗传学.北京:中国农业出版社,2005:101-104
26.Anderson C,Potter A A,Gerlach G F.Isolation and molecular characterization of spontaneously occurring cytolysin-negative mutants of Actinobacillus pleuropneumoniae serotype 7.Infect Immun,1991,59:4110-4116
27.Auger E,Deslandes V,Ramjeet M,Contreras I,Nash JH,Harel J,Gottschalk M,Olivier M,Jacques M.Host-pathogen interactions of Actinobacillus pleuropneumoniae with porcine lung and tracheal epithelial cells.Infect Immun,2009,77:1426-1441.
28.Baltes N,Hennig-Pauka I,Gedach G F.Both transferfin binding proteins are virulence factors in Actinobacillus pleuropneumoniae serotype 7 infection.FEMS Microbiol Lett,2002,209:283-287
29.Baltes N,Tonpitak W,Hennig-Pauka I,Gruber A D,Gedach G F.Actinobacillus pleuropneumoniae serotype 7 siderophore receptor FhuA is not required for virulence.FEMS Microbiol Lett,2003,220:41-48
30.Baudin A.,.Ozier-Kalogeropoulos,A.Denouel.A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae.Nucleic Acids Research,1993,21:3329-3330
31.Bei W,He Q,Yan L,Fang L,Tan Y,Xiao S,Zhou R,Jin M,Guo A,LV J,Huang H,Chen H.Construction and characterization of a live,attenuated apxⅡCA inactivation mutant of Actinobacillus pleuropneumoniae lacking a drug resistance marker.FEMS Microbiol Lett,2005,243:21-27
32.Bertram T A.Actinobacillus pleuropneumoniae:molecular aspects of virulence and pulmonary injury.Can J Vet Res,1990,54:53-56
33.Blackall P J,Klaasen H L,van den Bosch H,Kuhnert P,Frey J.Proposal of a new serovar of Actinobacillus pleuropneumoniae:serovar 15.Vet Microbiol,2002,84:47-52
34.Blanco M,Gutierrez-Martin C B,Rodriguez-Ferri E F,Roberts M C,Navas J. Distribution of tetracycline resistance genes in Actinobacillus pleuropneumoniae isolates from Spain.Antimicrob Agents Chemother,2006,50:702-708
35.Blanco M,Kadlec K,Gutierrez Martin C B,de la Fuente A J,Schwarz S,Navas J.Nucleotide sequence and transfer properties of two novel types of Actinobacillus pleuropneumoniae plasmids carrying the tetracycline resistance gene tet(H).J Antimicrob Chemother,2007,60:864-867
36.Boros I,Posfai G,Venetianer P High-copy-number derivatives of the plasmid cloning vector pBR322.Gene,1984,30:257-260
37.Bosse J T,Janson H,Sheehan B J,Beddek A J,Rycroft A N,Kroll J S,Langford P R.Actinobacillus pleuropneumoniae:pathobiology and pathogenesis of infection.Microbes Infect,2002,4:225-235
38.Bosse J T,MacInnes J I.Urease activity may contribute to the ability of Actinobacillus pleuropneumoniae to establish infection.Can J Vet Res,2000,64:145-150
39.Bosse J T,Nash J H,Kroll J S,Langford P R.Harnessing natural transformation in Actinobacillus pleuropneumoniae:a simple method for allelic replacements.FEMS Microbiol Lett,2004,233:277-281
40.Braun V.Iron uptake mechanisms and their regulation in pathogenic bacteria.Int J Med Microbiol,2001,291:67-79.
41.Briggs R E,Tatum F M.Generation and molecular characterization of new temperature-sensitive plasmids intended for genetic engineering of Pasteurellaceae.Appl Environ Microbiol,2005,71:7187-7195
42.Bunka S,Christensen C,Potter A A,Willson P J,Gerlach G F.Cloning and characterization of a protective outer membrane lipoprotein of Actinobacillus pleuropneumoniae serotype 5.Infect Immun,1995,63:2797-2800
43.Byrd W.Hooke A M.Temperature-sensitive mutants of Actinobacillus pleuropneumoniae induce protection in mice.Infect Immun,1997,65:2206-2210
44.Chai L L,Dave S W O,Steve K W O.Quantitative real-time polymerase chain reaction for determination of plasmid copy number in bacteria.Journal of Microbiological Method,2006,65:258-267
45.Chang C F,Yeh T M,Chou C C,Chang Y F,Chiang T S.Antimicrobial susceptibility and plasmid analysis of Actinobacillus pleuropneumoniae isolated in Taiwan.Vet Microbiol,2002,84:169-177
46.Chang Y F,Shi J,Shin S J,Lein D H.Sequence analysis of the ROB-1beta-lactamase gene from Actinobacillus pleuropneumoniae.Vet Microbiol,1992,32:319-325
47.Chen C Y,Nace G W,Solow B,Fratomico P.Complete nucleotide sequences of 84.5- and 3.2-kb plasmids in the multi-antibiotic resistant Salmonella enterica serovar Typhimurium U302 strain G8430,Plasmid,2007,57:29-43
48.Chen Y T,Shu H Y,Li L H,Liao T L,Wu K M,Shiau Y R,Su I J,Yan J J Tsai S F, Lauderdale T L.Complete nucleotide sequence of pK245,a 98-kilobase plasmid conferring quinolone resistance and extended-spectrum- beta- lactamase activity in a clinical Klebsiella pneumoniae isolate.Antimicrob Agents Chemother,2006,50:3861-3866.
49.Coppella S J,Acheson C M,Dhurjati P.Measurement of copy number using HPLC.Biotechnol Bioeng,1987,29:646-647
50.Datsenko K A,Wanner B L.One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.Proc Natl Acad Sci,2000,97:6640-6645
51.Deslandes V,Nash J H,Harel J,Coulton J W,Jacques M.Transcriptional profiling of Actinobacillus pleuropneumoniae under iron-restricted conditions.BMC Genomics,2007,13:68-72.
52.del Solar G,Giraldo R,Ruiz-Echevarria M J,Espinosa M,Diaz-Orejas.Replication and control of circular bacterial plasmids.Microbiol Mol Biol Rev,1998,62:434-464
53.Dixon LG,Albritton WL,Willson PJ.An analysis of the complete nucleotide sequence of the Haemophilus ducreyi broad-host-range plasmid pLS88.Plasmid,1994,32:228-232.
54.Dom P,Hommez J,Castryck F,Devriese L A,Haesebrouck F.Serotyping and quantitative determination of in vitro antibiotic susceptibility of Actinobacillus pleuropneumoniae strains isolated in Belgium(July 1991-August 1992).Vet Q,1994,16:10-13
55.Dreyfus A,Schaller A,Nivollet S,Segers R P,Kobisch M,Mieli L,Soerensen V,Hussy D,Miserez R,Zimmermann W,Inderbitzin F,Frey J.Use of recombinant ApxⅣ in serodiagnosis of Actinobacillus pleuropneumoniae infections,development and prevalidation of the ApxⅣ ELISA.Vet Microbiol,2004,99:227-238
56.Dubreuil J D,Jacques M,Mittal K R,Gottschalk M.Actinobacillus pleuropneumoniae surface polysaccharides:their role in diagnosis and immunogenicity.Anim Health Res Rev,2000,1:73-93
57.Fenwick B W,Osburn B I.Immune responses to the lipopolysaccharides and capsular polysaccharides of Haemophilus pleuropneumoniae in convalescent and immunized pigs.Infect Immun,1986,54:575-582
58.Fenwick B W,Osburn B I,Olander H J.Isolation and biological characterization of two lipopolysaccharides and a capsular-enriched polysaccharide preparation from Haemophilus pleuropneumoniae.Am J Vet Res,1986,47:1433-1441
59.Frey J.Virulence in Actinobacillus pleuropneumoniae and RTX toxins.Trends Microbiol,1995,3:257-261
60.Frey J,Bosse J T,Chang Y F,Cullen J M,Fenwick B,Gerlach G F,Gygi D,Haesebrouck F,Inzana T J,Jansen R.Actinobacillus pleuropneumoniae RTX-toxins:uniform designation of haemolysins,cytolysins,pleurotoxin and their genes.J Gen Microbiol,1993,139:1723-1728
61.Frey J,Kuhnert P,Villiger L,Nicolet J.Cloning and characterization of an Actinobacillus pleuropneumoniae outer membrane protein belonging to the family of PAL lipoproteins.Res Microbiol,1996,147:351-361
62.Frey J,Nicolet J.Hemolysin patterns of Actinobacillus pleuropneumoniae.J Clin MicrobioI,1990,28:232-236
63.Frey J,Nicolet J.Regulation of hemolysin expression in Actinobacillus pleuropneumoniae serotype 1 by Ca~(2+).Infect Immun,1988,56:2570-2575
64.Fuller C A,Yu R,Irwin S W,Schryvers A B.Biochemical evidence for a conserved interaction between bacterial transferrin binding protein A and transferrin binding protein B.Microb Pathog,1998,24:75-87
65.Fuller T E,Thacker B J,Duran C O,Mulks M H.A genetically-defined riboflavin auxotroph of Actinobacillus pleuropneumoniae as a live attenuated vaccine.Vaccine,2000,18:2867-2877
66.Gerami-Nejad M,Berman J,Gale C A.Cassettes for PCR-mediated construction of green,yellow,and cyan fluorescent protein fusions in Candida atbicans.Yeast,2001,18:859-864
67.Gerlach G F,Anderson C,Klashinsky S,Rossi-Campos A,Potter A A,Willson P J.Molecular characterization of a protective outer membrane lipoprotein(OmlA) from Actinobacillus pleuropneumoniae serotype 1.Infect Immun,1993,61:565-572
68.Gerlach G F,Klashinsky S,Anderson C,Potter A A,Willson P J.Characterization of two genes encoding distinct transferrin-binding proteins in different Actinobacillus pleuropneumoniae isolates.Infect Immun,1992,60:3253-3261
69.Gilbride K A,Rosendal S,Brunton J L.Plasmid mediated antimicrobial resistance in Ontario isolates of Actinobacillus(Haemophilus) pleuropneumoniae.Can J Vet Res.1989.53:38-42
70.Gonzalez G C,Caamano D L,Schryvers A B.Identification and characterization of a porcine-specific transferrin receptor in Actinobacillus pleuropneumoniae.Mol Microbiol,1990,4:1173-1179
71.Gonzalez G C,Yu R H,Rosteck P R,Jr.,Schryvers A B.Sequence,genetic analysis,and expression of Actinobacillus pleuropneumoniae transferrin receptor genes.Microbiology,1995,141:2405-2416
72.Gutierrez C B,Rodriguez Barbosa J I,Gonzalez O R,Tascon R I,Rodriguez Ferri E F.Viability of Actinobacillus pleuropneumoniae in frozen pig lung samples and comparison of different methods of direct diagnosis in fresh samples.Comp Immunol Microbiol Infect Dis,1992,15:89-95
73.Gutierrez C B,Rodriguez Barbosa J I,Tascon R I,Costa L,Riera P,Rodriguez Ferri E F.Serological characterisation and antimicrobial susceptibility of Actinobacillus pleuropneumoniae strains isolated from pigs in Spain.Vet Rec,1995,137:62-64
74.Habrun B,Bilic V,Humski A.Comparison of ELISA and 2-META assays used in serological diagnosis of infection with Actinobacillus pleuropneumoniae serotypes 2 and 4-7 in breeding pigs in Croatia.Prey Vet Med,1998b,36:179-186
75.Habrun B,Frey J,Bilic V,Nicolet J,Humski A.Prevalence of serotypes and toxin types of Actinobacillus pleuropneumoniae in pigs in Croatia.Vet Rec,1998a,143:255-256
76.Haesebrouck F,Chiers K,Van Overbeke I,Ducatelle R.Actinobacillus pleuropneumoniae infections in pigs:the role of virulence factors in pathogenesis and protection.Vet Microbiol,1997,58:239-249
77.Hamer-Barrera R,Godinez D,Enriquez VI,Vaca-Pacheco S,Martinez-Zunga R,Talamas-Rohana P,Suarez-G(u|¨)emez F,de la Garza M.Adherence of Actinobacillus pleuropneumoniae serptype 1 to swine buccal epithelial cell involves fibronectin.Can J Vet Res,2004,68:33-41
78.Hields M S,Reagin M J,Gerger R R.TOM new acrometic degradative plasmid from Burkholdena(Pseudomous) cepacia G4.Appl environ Microbiol,1995,61:1352-1356
79.Hinnebusch J,Barbour A G.Linear- and circular-plasmid copy numbers in Borrelia burgdorferi.J Bacteriol.1992,174:5251-5257.
80.Hirsh,D.C.,Martin,L.D.,Libal,M.C.Plasmid-mediated antimicrobial resistance in Haemophilus pleuropneumoniae.Am.J.Vet.Res,1982,43:269-272.
81.Huang H,Potter A A,Campos M,Leighton F A,Willson P J,Haines D M,Yates W D.Pathogenesis of porcine Actinobacillus pleuropneumonia,part Ⅱ:roles of proinflammatory cytokines.Can J Vet Res,1999,63:69-78
82.Husseiny M I,Hensel M.Evaluation of an intracellular-activated promoter for the generation of live Salmonella recombinant vaccines.Vaccine,2005,23:2580-2590.
83.Inzana T J.Capsules and virulence in the HAP group of bacteria.Can J Vet Res,1990,54:22-27
84.Inzana T J.Simplified procedure for preparation of sensitized latex particles to detect capsular polysaccharides:application to typing and diagnosis of Actinobacillus pleuropneumoniae.J Clin Microbiol,1995,33:2297-2303
85.Inzana T J,Ma J,Workman T,Gogolewski R P,Anderson P.Virulence properties and protective efficacy of the capsular polymer of Haemophilus(Actinobacillus)pleuropneumoniae serotype 5.lnfect Immun,1988,56:1880-1889
86.Inzana T J,Mathison B.Serotype specificity and immunogenicity of the capsular polymer of Haemophilus pleuropneumoniae serotype 5.Infect Immun,1987,55:1580-1587
87.Inzana T J,Todd J,Veit H P.Safety,stability,and efficacy of noncapsulated mutants of Actinobacillus pleuropneumoniae for use in live vaccines.Infect Immun,1993,61:1682-1686
88.Ishii H,Fukuyasu T,Iyobe S,Hashimoto H.Characterization of newly isolated plasmids from Actinobacillus pleuropneumoniae.Am J Vet Res,1993,54:701-708.
89.Ishii H,Hayashi F,Iyobe S,Hashimoto H.Characterization and classification of Actinobacillus(Haemophilus) pleuropneumoniae plasmids.Am J Vet Res.,1991,52:1816-1820.
90.Ishii H,Nakasone Y,Shigehara S,Honma K,Araki Y,Iyobe S,Hashimoto H.Drug-susceptibility and isolation of a plasmid in Haemophilus(Actinobacillus)pleuropneumoniae.Nippon Juigaku Zasshi,1990,52:1-9.
91.Ito H,Ishii H,Akiba M.Analysis of the complete nucleotide sequence of an Actinobacillus pleuropneumoniae streptomycin-sulfonamide resistance plasmid,pMS260.Plasmid,2004,51:41-47
92.Ito H,Uchida I,Sekizaki T,Ooishi E,Kawai T,Okabe T,Taneno A,Terakado N.Molecular cloning of an Actinobacillus pleuropneumoniae outer membrane lipoprotein(OmlA) from serotype 5a.Microb Pathog,1995,18:29-36
93.Jensen A E,Bertram T A.Morphological and biochemical comparison of virulent and avirulent isolates of Haemophilus pleuropneumoniae serotype 5.Infect Immun,1986,51:419-424
94.Jolie R A,Mulks M H,Thacker B J.Cross-protection experiments in pigs vaccinated with Actinobacillus pleuropneumoniae subtypes 1A and 1B.Vet.Microbiol,1995,45:383-391
95.Juteau J M,Sirois M,Medeiros A A,Levesque R C.Molecular distribution of ROB-1 beta-lactamase in Actinobacillus pleuropneumoniae.Antimicrob Agents Chemother,1991,35:1397-402.
96.Kamp E M,Popma J K,Anakotta J,Smits M A.Identification of hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae by use of monoclonal antibodies.Infect Immun,1991,59:3079-3085
97.Kamp E M,Popma J K,Van Leengoed L A.Serotyping of Haemophilus pleuropneumoniae in the Netherlands:with emphasis on heterogeneity within serotype 1 and(proposed) serotype 9.Vet Microbiol,1987,13:249-257
98.Kamp E M,Vermeulen T M,Smits M A,Haagsma J.Production of Apx toxins by field strains of Actinobacillus pleuropneumoniae and Actinobacillus suis.Infect Immun,1994,62:4063-4065
99.Kang M,Zhou R,Liu L,Langford P R,Chen H.Analysis of an Actinobacillus pleuropneumoniae multi-resistance plasmid,pHB0503.Plasmid,2009,61:135-139.
100.Karl Friehs.Plasmid Copy Number and Plasmid Stability.Adv Biochem Engin/Biotechnol,2004,86:47-82
101.Kawahara K,Kawase H,Nakai T,Kume K,Danbara H.Drug resistance plasmids of Actinobacillus(Haemophilus)pleuropneumoniae serotype 2 strains isolated from swine.Kitasato Arch Exp Med,1990,63:131-136.
102.Kehrenberg C,Meunier D,Targant H,Cloeckaert A,Schwarz S,Madec J Y.Plasmid-mediated florfenicol resistance in Pasteurella trehalosi.J Antimicrob Chemother,2006,58:13-17.
103.Kehrenberg C,Schulze-Tanzil G,Martel J L,Chashu-Dancla E,Schwarz S. Antimicrobial resistance in Pasteurella and Mannheimia:epidemiology and genetic basis.Vet.Res,2001,32:323-339.
104.Kehrenberg C,Schwarz S.Nucleotide sequence and organization of plasmid pMVSCS1 from Mannheimia varigena:identification of a multiresistance gene cluster.J.Antimicrob.Chemother,2002;49:383-386.
105.Kilian M,Nicolet J,and Biberstein E L.Biochemical and serological characterization of Haemophilus pleuropneumoniae(Matthews and Pattison,1961)Shope 1964 and proposal ofa neotype strain.Int.d.Syst.Bacteriol,1978;28:20-26.
106.Kiuchi A,Hara M,Tabuchi K.Drug resistant plasmid of Actinobacillus pleuropneumoniae isolated from swine pleuropneumonia in Thailand.Kansenshogaku Zasshi,1992,66:1243-1247.
107.Kraig E,Dailey T,Kolodrubetz D.Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans:homology to the alpha-hemolysin/leukotoxin gene family.Infect Immun,1990,58:920-929
108.Levonen K,Seppanen J,Veijalainen P.Antibodies against 12 serotypes of Actinobacillus pleuropneumoniae in finnish slaughter sows.Zentralbl Veterinarmed B,1996,43:489-495
109.Lin L,Bei W,Sha Y,Liu J,Guo Y,Liu W,Tu S,He Q,Chen H.Construction and immunogencity of a DeltaapxⅠC/DeltaapxⅡC double mutant of Actinobacillus pleuropneumoniae serovar 1.FEMS Microbiol Lett,2007,274:55-62
110.Li L,Zhou R,Li T,Kang M,Wan Y,Xu Z,Chen H.Enhanced biofilm formation and reduced virulence of Actinobacillus pleuropneumoniae luxS mutant.Microb Pathog.2008,45:192-200
111.Liu J,Chen X,Tan C,Guo Y,Chen Y,Fu S,Bei W,Chen H.Invivo induced RTX toxin ApxⅣA is essential for the full virulence of Actinobacillus pleuropneumoniae.Vet Microbiol.2009.[Epub ahead of print]
112.Livrelli V,Peduzzi J,Joly B.Sequence and molecular characterization of the ROB-1b-lactamase gene from Pasteurella haemolytica.Antimicrob Agents Chemother,1991,35:242-251.
113.Maas A,Jacobsen I D,Meens J,Gerlach G F.Use of an Actinobacillus pleuropneumoniae multiple mutant as a vaccine that allows differentiation of vaccinated and infected animals.Infect Immun,2006,74:4124-4132
114.Martin P R,Mulks M H.Cloning and characterization of a gene encoding an antigenic membrane protein from Actinobacillus pleuropneumoniae with homology to ABC transporters.FEMS Immunol Med Microbiol,1999,25:245-254
115.Matter D,Rossano A,Sieber S,Perreten V.Small multidrug resistance plasmids in Actinobacillus porcitonsillarum,Plasmid 2008,59:144-152
116.Mattick J S.Type Ⅳ pili and twitching motility.Annu Rev Microbiol,2002,56:289-314
117.Maudsley J R,Kadis S,Mayberry W R.Isolation,purification,and partial characterization of a lipopolysaccharide from Haemophilus pleuropneumoniae. Infect Immun, 1986, 51: 501-506
118. Mayer M P A new set of useful cloning and expression vectors derived from pBlueScript. Gene, 1995 ,163: 41-46
119. Mikael L G, Pawelek P D, Labrie J, Sirois M, Coulton J W, Jacques M. Molecular cloning and characterization of the ferric hydroxamate uptake (fhu) operon in Actinobacillus pleuropneumoniae. Microbiology, 2002,148: 2869-2882.
120. Mikael L G, Srikumar R, Coulton J W, Jacques M. fhuA of Actinobacillus pleuropneumoniae encodes a ferrichrome receptor but is not regulated by iron. Infect Immun, 2003, 71: 2911-2915.
121. Miller C A, Cohen S N. The partition (par) locus of pSC101 is an enhancer of plasmid incompatibility. Mol Microbiol, 1993, 9: 695-702
122. Min K, Chae C. Serotype and apx genotype profiles of Actinobacillus pleuropneumoniae field isolates in Korea. Vet Rec, 1999, 145: 251-254
123. Mittal K R, Higgins R, Lariviere S, Nadeau M. Serological characterization of Actinobacillus pleuropneumoniae strains isolated from pigs in Quebec. Vet Microbiol, 1992, 32: 135-148
124. Mulks M H, Moxon E R, Bricker J, Wright A, Plaut A G. Examination of Haemophilus pleuropneumoniae for immunoglobulin A protease activity. Infect Immun, 1984,45: 276-277
125. Murphy K C. Use of bacteriophage lambda recombination functions to promote gene replacement in Escherichia coli. J Bacteriol, 1998, 180: 2063-2071.
126. Murray I A, Hawkins A R, Keyte J W, Shaw W V. Nucleotide sequence analysis and overexpression of the gene encoding a type III chloramphenicol acetyltransferase. Biochem J, 1988,252: 173-179.
127. Muyrers J P, Zhang Y, Testa G, Stewart A F. Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Res, 1999, 27: 1555-1557.
128. Negrete-Abascal E, Reyes M E, Garcia R M, Vaca S, Giron J A, Garcia O, Zenteno E, De La Garza M. Flagella and Motility in Actinobacillus pleuropneumoniae. J Bacteriol, 2003, 185: 664-668
129. Negrete-Abascal E, Tenorio V R, Guerrero A L, Garcia R M, Reyes M E, de la Garza M. Purification and characterization of a protease from Actinobacillus pleuropneumoniae serotype 1, an antigen common to all the serotypes. Can J Vet Res, 1998,62:183-190
130. Negrete-Abascal E, Tenorio V R, Serrano J J, Garcia C, de la Garza M. Secreted proteases from Actinobacillus pleuropneumoniae serotype 1 degrade porcine gelatin, hemoglobin and immunoglobulin A. Can J Vet Res, 1994, 58: 83-86
131. Nielsen R. Haemophilus pleuropneumoniae serotypes-cross protection experiments. Nord Vet Med, 1984, 36: 221-234
132. Nielsen R, Andresen L O, Plambeck T, Nielsen J P, Krarup L T, Jorsal S E. Serological characterization of Actinobacillus pleuropneumoniae biotype 2 strains isolated from pigs in two Danish herds. Vet Microbiol, 1997, 54: 35-46
133. Nina B, Walaiporn T, Gerlald F.G, et al. Actinobacillus pleuropneumoniae iron transport and crease activity:effects on bacterial virulence and host immune response. Infect.Immun, 2001, 69: 472-478.
134. Novick R P. Plasmid incompatibility. Microbiol Rev. 1987; 51: 381-395
135. Oswald W, Tonpitak W, Ohrt G, Gerlach G. A single-step transconjugation system for the introduction of unmarked deletions into Actinobacillus pleuropneumoniae serotype 7 using a sucrose sensitivity marker. FEMS Microbiol Lett, 1999, 179: 153-160
136. Paulsson J, Ehrenberg M. Molecular clocks reduce plasmid loss rates: the R1 case. J Mol Biol, 2000, 297: 179-192
137. Pagotto F, Dillon JAMultiple origins and replication proteins influence biological properties of beta-lactamase-producing plasmids from Neisseria gonorrhoeae. J Bacteriol. 2001, 183: 5472-5481.
138. Pawelek P D, Coulton J W. Hemoglobin-binding protein HgbA in the outer membrane of Actinobacillus pleuropneumoniae: homology modelling reveals regions of potential interactions with hemoglobin and heme. J Mol Graph Model, 2004,23:211-221
139. Perry M B. Structural analysis of the lipopolysaccharide of Actinobacillus (Haemophilus) pleuropneumoniae serotype 10. Biochem Cell Biol, 1990, 68:808-810
140. Poteete A R, Fenton A C, Murphy K C. Roles of RuvC and RecG in phage lambda red-mediated recombination. J Bacteriol, 1999,181: 5402-5408.
141. Power S B, Quigley F C, Pritchard D G, Croston P. Porcine pleuropneumonia associated with Haemophilus pleuropneumoniae serotype 3 in the Republic of Ireland. Vet Rec, 1983, 113: 113-114
142. Projan S J, Carleton S, Novick R P. Determination of plasmid copy number by fluorescence densitometry. Plasmid, 1983, 9: 182-190
143. Pushnova E A , Geier M , Zhu Y S. An easy and accurate agarose gelassay for quantitation of bacterial plasmid copy numbers. Anal Biochem, 2000, 284: 70—76.
144. Rather P N, Mann P A, Mierzwa R Miller G H, Shaw K J. Analysis of the aac(3)-VIa gene encoding a novel 3-N-acetyltransferase. Antimicrob Agents Chemother, 1993, 37: 2074-2079
145. Redfield R J, Findlay W A, Bosse J, Kroll J S, Cameron A D, Nash J H. Evolution of competence and DNA uptake specificity in the Pasteurellaceae. BMC Evol Biol, 2006, 6: 82
146. Rioux S, Begin C, Dubreuil J D, Jacques M. Isolation and characterization of LPS mutants of Actinobacillus pleuropneumoniae serotype 1. Curr Microbiol, 1997, 35: 139-144
147. Rioux S, Galarneau C, Harel J, Frey J, Nicolet J, Kobisch M, Dubreuil J D, Jacques M. Isolation and characterization of mini-Tn10 lipopolysaccharide mutants of Actinobacillus pleuropneumoniae serotype 1. Can J Microbiol, 1999,45: 1017-1026
148. Rioux S, Galarneau C, Harel J, Kobisch M, Frey J, Gottschalk M, Jacques M. Isolation and characterization of a capsule-deficient mutant of Actinobacillus pleuropneumoniae serotype 1. Microb Pathog, 2000,28: 279-289
149. Sambrook J, Russell D W. Molecular cloning: a laboratory manual (Third Edition). New York: Cold Spring Harbor Press, 2001.
150. San Millan A, Escudero J A., Catalan A, Nieto S, Farelo F, Gibert M, Moreno M A, Domingnesc L. P-lactam resistance in Haemophilus parasuis is mediated by plasmid pB1000 bearing blaROB-1. Antimicrob. Agents Chemother 2007; 51: 2260- 2264
151. Satran P, Nedbalcova K. Prevalence of serotypes, production of Apx toxins, and antibiotic resistance in strains of Actinobacillus pleuropneumoniae isolated in the Czech Republic. Vet Med, 2002,47: 92-98
152. Schaller A, Djordjevic SP, Eamens GJ, Forbes W A, Kuhu R, Gonzale-zorn B, Kuhnerto P, Gottschalk M, Nicolet J. Identification and detection of Actinobacillus pleuropneumoniae by PCR based on the gene apxIVA. Vet Microbiol., 2001, 79: 47-62.
153. Scholz P, Haring V, Wittmann-Liebold B, Ashman K, Bagdasarin M, Scherzinger E, Frey J. Complete nucleotide sequence and gene organization of the broad-host-range plasmid RSF1010. Gene, 1989, 75: 271-88.
154. Shakarji L, Mikael L G, Srikumar R, Kobisch M, Coulton J W, Jacques M. Fhua and HgbA, outer membrane proteins of Actinobacillus pleuropneumoniae: their role as virulence determinants. Can J Microbiol, 2006, 52: 391-396
155. Sheehan B J, Bosse J T, Beddek A J, Rycroft A N, Kroll J S, Langford P R. Identification of Actinobacillus pleuropneumoniae genes important for survival during infection in its natural host. Infect Immun, 2003, 71: 3960-3970
156. Srikumar R, Mikael L G, Pawelek P D, Khamessan A, Gibbs B F, Jacques M, Coulton J W. Molecular cloning of haemoglobin-binding protein HgbA in the outer membrane of Actinobacillus pleuropneumoniae. Microbiology, 2004, 150: 1723-1734
157. Strathdee C A, Lo R Y. Cloning, nucleotide sequence, and characterization of genes encoding the secretion function of the Pasteurella haemolytica leukotoxin determinant. J Bacteriol, 1989, 171: 916-928
158. Susan E.H.West, Mary Jo M. Construction of Actinobacillus pleuropneumoniae-Escherichia coli cosmid cloning vector. Gene, 1995, 160:87-88
159. Susan E.H.West, Mary Jo M.Romero, Laura B.Regassa, Nicolette .A. Construction of Actinobacillus pleuropneumoniae-Escherichia coli shuttle vector:expression of antibiotic-resistance genes. Gene, 1995, 160: 81-86
160. Tadjine M, Mittal K R. Study of antigenic heterogeneity among Actinobacillus pleuropneumoniae serotype 7 strains.Vet Microbiol,2001,78:49-60
161.Takamatsu D,Osaki M,Sekizaki T.Thermosensitive suicide vectors for gene replacement in Streptococcus suis.Plasmid,2001,46:140-148
162.Tang J,Zhou R,Shi X,Kang M,Wang H,Chen H.Two thermostable nucleases coexisted in Staphylococcus aureus:evidence from mutagenesis and in vitro expression.FEMS Microbiol Lett,2008,284:176-183
163.Tascon Cabrero R I,Vazquez-Boland J A,Gutierrez C B,Rodriguez-Barbosa J I,Rodriguez-Ferri E F.Actinobacillus pleuropneumoniae does not require urease activity to produce acute swine pleuropneumonia.FEMS Microbiol Lett,1997,148:53-57
164.Tascon R I,Rodriguez-Ferri E F,Gutierrez-Martin C B,Rodriguez-Barbosa I,Berche P,Vazquez-Boland J A.Transposon mutagenesis in Actinobacillus pleuropneumoniae with a Tn10 derivative.J Bacteriol,1993,175:5717-5722
165.Tascon R I,Vazquez-Boland J A,Gutierrez-Martin C B,Rodriguez-Barbosa I,Rodriguez-Ferri E F.The RTX haemolysins ApxⅠ and ApxⅡ are major virulence factors of the swine pathogen Actinobacillus pleuropneumoniae:evidence from mutational analysis.Mol Microbiol,1994,14:207-216
166.Tonpitak W,Baltes N,Hennig-Pauka I,Gerlach G F.Construction of an Actinobacillus pleuropneumoniae serotype 2 prototype live negative-marker vaccine.Infect Immun,2002,70:7120-7125
167.Tracy E,Ye F,Baker B D,Munson R S Jr.Construction of non-polar mutants in Haemophilus influenzae using FLP recombinase technology.BMC Mol Biol,2008,9:101
168.Turni C,Blackall P J.An evaluation of the apxⅣA based PCR-REA method for differentiation of Actinobacillus pleuropneumoniae.Vet Microbiol,2007,121:163-169
169.Udeze F A,Latimer K S,Kadis S.Role of Haemophilus pleuropneumoniae lipopolysaccharide endotoxin in the pathogenesis of porcine Haemophilus pleuropneumonia.Am J Vet Res,1987,48:768-773
170.U.N streips and R.E.Yasbin,Modem Microbial Genetics,Wileyliss Inc,1991
171.van den Bosch H,Frey J.Interference of outer membrane protein PalA with protective immunity against Actinobacillus pleuropneumoniae infections in vaccinated pigs.Vaccine,2003,21:3601-3607
172.Vigre H,Angen O,Barfod K,Lavritsen D T,Sorensen V.Transmission of Actinobacillus pleuropneumoniae in pigs under field-like conditions:emphasis on tonsillar colonisation and passively acquired colostral antibodies.Vet Microbiol,2002,89:151-159
173.Vliegenthart J S,Ketelaar-van Gaalen P A,van de Klundert J A.Nucleotide sequence of the aacC3 gene,a gentamicin resistance determinant encoding aminoglycoside-(3)-N-acetyltransferase Ⅲ expressed in Pseudomonas aeruginosa but not in Escherichia coli.Antimicrob Agents Chemother,1991,35:892-897
174.Ward A C,Hillier A J,Davidson B E,Powell I B.Stability analysis of the Lactococcus lactis DRC1 lactose plasmid using pulsed-field gel electrophoresis.Plasmid,1993,29:70-3.
175.Ward C K,Inzana T J.Resistance of Actinobacillus pleuropneumoniae to bactericidal antibody and complement is mediated by capsular polysaccharide and blocking antibody specific for lipopolysacchadde.J Immunol,1994,153:2110-2121
176.Wandersman C,Stojiljkovic I.Bacterial heme sources:the role of heme,hemoprotein receptors and hemophores.Curr Opin Microbiol,2000,3:215-220.
177.Welch R A.Pore-forming cytolysins of gram-negative bacteria.Mol Microbiol,1991,5:521-528
178.Willson P J,Deneer H G,Potter A,Albritton W.Characterization of a streptomycin-sulfonamide resistance plasmid from Actinobacillus pleuropneumoniae Antimicrob Agents Chemother,1989,33:235-238
179.Wright C L,Strugnell R A,Hodgson A L.Characterization of a Pasteurella multocida plasmid and its use to express recombinant proteins in P.multocida.Plasmid,1997,37:65-79.
180.Xu F,Chen X,Shi A,Yang B,Wang J,Li Y,Guo X,Blackall P J,Yang H.Characterization and immunogenicity of an apxⅠA mutant of Actinobacillus pleuropneumoniae.Vet Microbiol,2006,118:230-239
181.Xu Z,Zhou Y,Li L,Zhou R,Xiao S,Wan Y,Zhang S,Wang K,Li W,Li L,Jin H,Kang M,Dalai B,Li T,Liu L,Cheng Y,Zhang L,Xu T,Zheng H,Pu S,Wang B,Gu W,Zhang XL,Zhu GF,Wang S,Zhao GP,Chen H.Genome biology of Actinobacillus pleuropneumoniae JL03,an isolate of serotype 3 prevalent in China.PLoS ONE,2008,3:e1450.
182.Ying-Tsong Chen,Hung-Yu Shu,Ling-Hui Li,Tsai-Lien Liao,Keh-Ming Wu,Yih-Ru Shiau,4 Jing-Jou Yan,Ih-Jen Su,Shih-Feng Tsai,and Tsai-Ling Lauderdale..Complete Nucleotide Sequence of pK245,a 98-Kilobase Plasmid Conferring Quinolone Resistance and Extended-Spectnum-Lactamase Activity in a Clinical Klebsiella pneumoniae Isolate.Antimicrob Agents Chemother,2006,50:3861-3866,