羊种布鲁氏菌感染胚胎滋养层细胞的分子机制研究
摘要
布鲁氏菌病(简称布病)是由布鲁氏菌引起的一类动物源性人兽共患病,在世界范围内广泛流行,尤其是发展中国家。近几年回升势头迅猛,引起了世界范围的广泛关注,为此,我国紧急发布了《关于加强布鲁氏菌防治工作的通知》。布鲁氏菌是一种兼性胞内寄生致病菌,侵袭力强、传染途径多,人感染后呈持续性感染,目前尚无法根治；家畜感染后主要引发母畜流产,给畜牧业生产造成严重损失。动物胎盘中含有大量的赤藓醇,能够促进布鲁氏菌的生长,布鲁氏菌对胎盘具有显著的亲嗜性,胚胎滋养细胞是母体和胎儿的联系纽带,同时也是布鲁氏菌感染的靶细胞,一旦受到损伤,就会导致流产,但引发流产的分子机制还不清楚。为此,本研究以布鲁氏菌和胚胎滋养层细胞为研究对象,主要展开以下的研究工作：
1.羊种布鲁氏菌的分离鉴定及ELISA检测方法的建立。通过采用细菌群体形态观察、PCR、生化试验对分离培养的菌株进行鉴定,获得了羊种布鲁氏菌生物3型1株,命名为027株,对其SP41基因进行克隆、表达、纯化,包被酶标反应板并进行样本检测。结果布鲁氏菌病间接ELISA检测方法的最优条件是重组蛋白SP41最佳抗原包被浓度为0.6μg/mL,最佳血清稀释度为1：50,该方法重复性好、特异性强,样本阳性检出率高于虎红平板试验和试管凝集试验。
2.羊种布鲁氏菌ery操纵子在感染人胚胎滋养层细胞HPT-8过程中的表达调控。采用实时定量PCR方法检测了布鲁氏菌侵染HPT-8细胞过程中ery操纵子4个基因在未侵染、侵染20min、1h、2h、3h、4h时的表达差异,结果ery操纵子在侵染前后的表达有明显差异,eryA、eryB、eryC相对表达量在侵染2h时表达量最高,eryD在3h时的相对表达量最高,其余状态下的表达量都很低,并且随着eryD表达量升高,eryA、eryB、eryC的表达量降低。
3.建立羊种布鲁氏菌027株侵染HPT-8细胞的cDNA文库。分别提取布鲁氏菌侵染20min、1h、2h、3h、4h后HPT-8细胞总RNA,逆转录合成cDNA,同源重组法构建布鲁氏菌侵染HPT-8细胞的cDNA文库,并对部分EST进行测序分析,结果羊种布鲁氏菌027株侵染人滋养层cDNA文库的库容为1.43×106,重组率为96.92%,插入片段大小在0.2-5kb；对文库63个克隆进行测序,用BlastX和BlastN进行序列同源性比对,并将63个基因进行了功能分类。然后,构建pGBKT7-omp25诱饵质粒,转化酵母Y187,结果表明诱饵菌无自激活活性、无毒性。
4.筛选并验证与布鲁氏菌流产相关因子互作的HPT-8细胞靶蛋白。采用酵母双杂交技术筛选与布鲁氏菌外膜蛋白OMP25互作的HPT-8细胞捕获蛋白,并采用免疫共沉淀技术验证互作的蛋白。共筛选出了7个与布鲁氏菌OMP25诱饵蛋白相结合阳性捕获蛋白,验证试验表明布鲁氏菌外膜蛋白OMP25与HPT-8细胞的Ferritin、hypothetical LOC339123蛋白发生了相互作用。
5.分析捕获蛋白在布鲁氏菌侵染HPT-8细胞过程中的作用。根据铁蛋白、hypothetical LOC339123蛋白核苷酸序列,分别构建了3个特异性shRNA干扰载体,转染HPT-8细胞,实时定量PCR检测2个基因的表达水平,检验其干扰效率；采用布鲁氏菌感染转染shRNA干扰载体前、后的HPT-8细胞,检测布鲁氏菌的相对数量。结果针对铁蛋白、hypothetical LOC339123合成的shRNA干扰片段与各自的混合组的干扰效果基本一致,Ferritin混合组的干扰抑制率为76.18%, hypothetical LOC339123混合组的干扰抑制率为71.11%。针对铁蛋白的干扰载体混合组转染前后,布鲁氏菌相对数量差异较大,而hypotheticalLOC339123的差异不明显。
以上研究结果表明,分离培养的布鲁氏菌027株为羊种布鲁氏菌生物3型；成功构建了基于重组蛋白SP41的布鲁氏菌病间接ELISA检测方法；布鲁氏菌感染HPT-8细胞过程中ery操纵子4个基因在不同时间点表达存在着差异；成功构建了羊种布鲁氏菌027株侵染HPT-8细胞的cDNA文库；布鲁氏菌OMP25蛋白与HPT-8细胞的Ferritin、hypothetical LOC339123发生了相互作用,Ferritin与布鲁氏菌感染相关,hypothetical LOC339123与布鲁氏菌感染不相关。通过本研究,为揭示布鲁氏菌引发流产的分子机制提供线索,也为布鲁氏菌病新药物研发、防治及家畜抗病育种工作奠定基础。
Brucellosis is a zoonotic disease caused by members of the genus Brucella. It is widely popular in the world, especially in developing countries. Recently, the rapid increasing cases in human and animals have caused widespread concern around the world. China released an emergent document "on the strengthening of prevention and treatment of Brucellosis notice". Brucella is a facultative intracellular parasitic bacterium. Due to its strong invasion and multiple approaches of transmission, patients show persistent infection, which is usually known as incurable disease. Infectious animal mainly caused abortion, which leads to serious loss for livestock industry. Animal placenta contains much Erythritol, which can promote the growth of Brucella. Embryonic trophoblast, knows as target cell of brucella, is a link between the pregnant animal and the fetus. Once infected, it will lead to abortion. However, its molecular mechanism of abortion is unclear. In this study, based on Brucella and embryonic trophoblast cells, the main research work carried out as the follows:
1. Isolation and Identification of Brucella melitensis and ELISA method were constructed. According to bacterial morphology, PCR, biochemical examination, Brucella melitensis type 3, named as 027 strain, was obtained. After its SP41 gene was cloned, expressed, purified, indirect ELISA method was built. During our experiments, the best concentration of SP41 recombinant protein is 0.6μg/mL, the best dilution of serum is 1:50. The method has good reproducibility, specificity, positive rate of samples was higher than the rose Bengal plate test (RBPT) and standard tube agglutination test(SAT).
2. Study on ery operon expression and regulation of Brucella melitensis during human embryonic trophoblast HPT-8 infected with pathogen. The real-time quantitative PCR method was used to detect expression differences of ery operon 4 genes in non-infected, infected 20min, 1h,2h,3h, and 4h. ery A, eryB and eryC in 2h has a significant over-expression. eryD in 3h has the highest expression compared to ery A, eryB and eryC. Interestingly, with the increase of eryD expression, ery A, eiyB and eryC decreased.
3. The cDNA library of HPT-8 cells infected with Brucella melitensis 027 strain was constructed. The total RNA of infected cells at 20min, 1h,2h,3h and 4h Were extracted respectively. With cDNA synthesized by reverse transcriptase, homologous recombination construct infected HPT-8 cell cDNA library. The partial ESTs were sequenced. The results showed that cDNA library was successfully constructed. cDNA capacity was 1.43×106, the recombinant rate was 96.92 percent. The size of the inserted fragments is between 0.2-5kb.63 clones of cDNA library were random selected and sequenced. These gene were classified by BlastX and BlastN. The bait plasmid pGBKT7-omp25 was constructed into yeast Y187, which results show that the bait yeast is non-self-activated and non-toxic.
4. The target protein were screened and verified. OMP25 interacted with 7 positive protein of HPT-8 cells by yeast two-hybrid. Ferritin and hypothetical LOC339123 were verified by immunoprecipitation.
5. Study on the function of prey protein. According to nucleotide sequences of ferritin and hypothetical LOC339123, three specific interfering shRNA vectors transfecting HPT-8 cells, respectively, real-time quantitative PCR detected. Ferritin mixed group interference suppression rate of 76.18%, hypothetical LOC339123 mixed group interference suppression rate of 71.11%. After Ferritin was interfered, the relative number of Brucella in HPT-8 cells increased compared to hypothetical LOC339123 protein.
The above results show that the isolate was Brucella melitensis type 3; indirect ELISA based on SP41 was successfully built; Brucella ery operon 4 genes expression differed at different times during infecting HPT-8 cells; The cDNA library of HPT-8 cells infected with Brucella melitensis 027 strain was successfully constructed; Brucella OMP25 interacted with HPT-8 Cell's ferritin and hypothetical LOC339123 protein; ferritin is related to Brucella infection while hypothetical LOC339123 protein is not. In this study, It is useful to demonstrate molecular mechanism of abortion, to screen specific candidate drugs to brucellosis, to give a upstream work for breeding of anti-brucellosis livestock.
1.羊种布鲁氏菌的分离鉴定及ELISA检测方法的建立。通过采用细菌群体形态观察、PCR、生化试验对分离培养的菌株进行鉴定,获得了羊种布鲁氏菌生物3型1株,命名为027株,对其SP41基因进行克隆、表达、纯化,包被酶标反应板并进行样本检测。结果布鲁氏菌病间接ELISA检测方法的最优条件是重组蛋白SP41最佳抗原包被浓度为0.6μg/mL,最佳血清稀释度为1：50,该方法重复性好、特异性强,样本阳性检出率高于虎红平板试验和试管凝集试验。
2.羊种布鲁氏菌ery操纵子在感染人胚胎滋养层细胞HPT-8过程中的表达调控。采用实时定量PCR方法检测了布鲁氏菌侵染HPT-8细胞过程中ery操纵子4个基因在未侵染、侵染20min、1h、2h、3h、4h时的表达差异,结果ery操纵子在侵染前后的表达有明显差异,eryA、eryB、eryC相对表达量在侵染2h时表达量最高,eryD在3h时的相对表达量最高,其余状态下的表达量都很低,并且随着eryD表达量升高,eryA、eryB、eryC的表达量降低。
3.建立羊种布鲁氏菌027株侵染HPT-8细胞的cDNA文库。分别提取布鲁氏菌侵染20min、1h、2h、3h、4h后HPT-8细胞总RNA,逆转录合成cDNA,同源重组法构建布鲁氏菌侵染HPT-8细胞的cDNA文库,并对部分EST进行测序分析,结果羊种布鲁氏菌027株侵染人滋养层cDNA文库的库容为1.43×106,重组率为96.92%,插入片段大小在0.2-5kb；对文库63个克隆进行测序,用BlastX和BlastN进行序列同源性比对,并将63个基因进行了功能分类。然后,构建pGBKT7-omp25诱饵质粒,转化酵母Y187,结果表明诱饵菌无自激活活性、无毒性。
4.筛选并验证与布鲁氏菌流产相关因子互作的HPT-8细胞靶蛋白。采用酵母双杂交技术筛选与布鲁氏菌外膜蛋白OMP25互作的HPT-8细胞捕获蛋白,并采用免疫共沉淀技术验证互作的蛋白。共筛选出了7个与布鲁氏菌OMP25诱饵蛋白相结合阳性捕获蛋白,验证试验表明布鲁氏菌外膜蛋白OMP25与HPT-8细胞的Ferritin、hypothetical LOC339123蛋白发生了相互作用。
5.分析捕获蛋白在布鲁氏菌侵染HPT-8细胞过程中的作用。根据铁蛋白、hypothetical LOC339123蛋白核苷酸序列,分别构建了3个特异性shRNA干扰载体,转染HPT-8细胞,实时定量PCR检测2个基因的表达水平,检验其干扰效率；采用布鲁氏菌感染转染shRNA干扰载体前、后的HPT-8细胞,检测布鲁氏菌的相对数量。结果针对铁蛋白、hypothetical LOC339123合成的shRNA干扰片段与各自的混合组的干扰效果基本一致,Ferritin混合组的干扰抑制率为76.18%, hypothetical LOC339123混合组的干扰抑制率为71.11%。针对铁蛋白的干扰载体混合组转染前后,布鲁氏菌相对数量差异较大,而hypotheticalLOC339123的差异不明显。
以上研究结果表明,分离培养的布鲁氏菌027株为羊种布鲁氏菌生物3型；成功构建了基于重组蛋白SP41的布鲁氏菌病间接ELISA检测方法；布鲁氏菌感染HPT-8细胞过程中ery操纵子4个基因在不同时间点表达存在着差异；成功构建了羊种布鲁氏菌027株侵染HPT-8细胞的cDNA文库；布鲁氏菌OMP25蛋白与HPT-8细胞的Ferritin、hypothetical LOC339123发生了相互作用,Ferritin与布鲁氏菌感染相关,hypothetical LOC339123与布鲁氏菌感染不相关。通过本研究,为揭示布鲁氏菌引发流产的分子机制提供线索,也为布鲁氏菌病新药物研发、防治及家畜抗病育种工作奠定基础。
Brucellosis is a zoonotic disease caused by members of the genus Brucella. It is widely popular in the world, especially in developing countries. Recently, the rapid increasing cases in human and animals have caused widespread concern around the world. China released an emergent document "on the strengthening of prevention and treatment of Brucellosis notice". Brucella is a facultative intracellular parasitic bacterium. Due to its strong invasion and multiple approaches of transmission, patients show persistent infection, which is usually known as incurable disease. Infectious animal mainly caused abortion, which leads to serious loss for livestock industry. Animal placenta contains much Erythritol, which can promote the growth of Brucella. Embryonic trophoblast, knows as target cell of brucella, is a link between the pregnant animal and the fetus. Once infected, it will lead to abortion. However, its molecular mechanism of abortion is unclear. In this study, based on Brucella and embryonic trophoblast cells, the main research work carried out as the follows:
1. Isolation and Identification of Brucella melitensis and ELISA method were constructed. According to bacterial morphology, PCR, biochemical examination, Brucella melitensis type 3, named as 027 strain, was obtained. After its SP41 gene was cloned, expressed, purified, indirect ELISA method was built. During our experiments, the best concentration of SP41 recombinant protein is 0.6μg/mL, the best dilution of serum is 1:50. The method has good reproducibility, specificity, positive rate of samples was higher than the rose Bengal plate test (RBPT) and standard tube agglutination test(SAT).
2. Study on ery operon expression and regulation of Brucella melitensis during human embryonic trophoblast HPT-8 infected with pathogen. The real-time quantitative PCR method was used to detect expression differences of ery operon 4 genes in non-infected, infected 20min, 1h,2h,3h, and 4h. ery A, eryB and eryC in 2h has a significant over-expression. eryD in 3h has the highest expression compared to ery A, eryB and eryC. Interestingly, with the increase of eryD expression, ery A, eiyB and eryC decreased.
3. The cDNA library of HPT-8 cells infected with Brucella melitensis 027 strain was constructed. The total RNA of infected cells at 20min, 1h,2h,3h and 4h Were extracted respectively. With cDNA synthesized by reverse transcriptase, homologous recombination construct infected HPT-8 cell cDNA library. The partial ESTs were sequenced. The results showed that cDNA library was successfully constructed. cDNA capacity was 1.43×106, the recombinant rate was 96.92 percent. The size of the inserted fragments is between 0.2-5kb.63 clones of cDNA library were random selected and sequenced. These gene were classified by BlastX and BlastN. The bait plasmid pGBKT7-omp25 was constructed into yeast Y187, which results show that the bait yeast is non-self-activated and non-toxic.
4. The target protein were screened and verified. OMP25 interacted with 7 positive protein of HPT-8 cells by yeast two-hybrid. Ferritin and hypothetical LOC339123 were verified by immunoprecipitation.
5. Study on the function of prey protein. According to nucleotide sequences of ferritin and hypothetical LOC339123, three specific interfering shRNA vectors transfecting HPT-8 cells, respectively, real-time quantitative PCR detected. Ferritin mixed group interference suppression rate of 76.18%, hypothetical LOC339123 mixed group interference suppression rate of 71.11%. After Ferritin was interfered, the relative number of Brucella in HPT-8 cells increased compared to hypothetical LOC339123 protein.
The above results show that the isolate was Brucella melitensis type 3; indirect ELISA based on SP41 was successfully built; Brucella ery operon 4 genes expression differed at different times during infecting HPT-8 cells; The cDNA library of HPT-8 cells infected with Brucella melitensis 027 strain was successfully constructed; Brucella OMP25 interacted with HPT-8 Cell's ferritin and hypothetical LOC339123 protein; ferritin is related to Brucella infection while hypothetical LOC339123 protein is not. In this study, It is useful to demonstrate molecular mechanism of abortion, to screen specific candidate drugs to brucellosis, to give a upstream work for breeding of anti-brucellosis livestock.
引文
[1]Corbel MJ, Brinley-Morgan WJ. Genus Brucella:Bergey's Manual of Systematic. Bacteriology,1976,1:377-388.
[2]WHO/FAO. The Development of New/Improved Brucellosis Vaccines:Report of WHO Meeting. Geneva Switzerland,1997,1-48.
[3]Cvjetanovic B, Ikic D, Lane WR, et al. Studies of combined quadruple vaccines against diphtheria, pertussis, tetanus, and typhoid fever:reactogenicity and antigenicity. Bull World Health Organ,1972,46(1):47-52.
[4]Ross HM, Jahans KL, MacMillan AP, et al. Brucella species infection in North Sea seal and cetacean populations. Vet Rec,1996,138:647-648.
[5]Claire E Dawson, Emma J Stubberfield, Lorraine L Perrett. Phenotypic and molecular characterisation of Brucella isolates from marine mammals. BMC Microbiology,2008,8:224.
[6]Maquart M, Zygmunt MS, Cloeckaert A. Marine mammal Brucella isolates with different genomic characteristics display a differential response when infecting human macrophages in culture. Microbes Infect,2009,11(3):361-366.
[7]Emilie Fugier, Georgios Pappas, Jean-Pierre Gorvel. Virulence factors in brucellosis:implications for aetiopathogenesis and treatment. Expert Rev Mol Med,2007,9(35):10.1017/S1462399407000543.
[8]刘志文,廖礼维,王莹,等.新疆绵羊种布鲁氏菌的首次分离和鉴定.中国兽医杂志,1983,6：5-7.
[9]张高轩,张银国,刘志文,等.恒河猴人工感染BRUCELLA OVIS后病理学观察及病原回收.中国人兽共患病杂志,1999,15(4)：78-80.
[10]Baldwin CL, AJ Winter. Macrophages and Brucella. Immunol,1994,60:363-80.
[11]Lenntte EH, A Balows, William J, et al. Manual of clinical microbiology. American Society for Microbiology,1985,434-441.
[12]毛开荣.动物布鲁氏菌病防治技术研究进展.中国兽药杂志,2003,(9)：37-40.
[13]Scholz HC, Hubalek Z, Sedlacek I, et al. Brucella microtispnov isolated from the common vole Microtus arvalis. Int J Syst Evol Microbiol,2008,58:375-382.
[14]McDonald WL, Jamaludin R, Mackereth G, et al. Characterization of a Brucella spp. strain as a marine-mammal type despite isolation from apatient with spinal osteomyelitis in New Zealand. J Clin Microbiol,2006,44:4363-4370.
[15]Whatmore AM, Dawson CE, Groussaud P, et al. A marine mammal Brucella genotype associated with zoonotic infection. Emerg Infect Dis,2008,14: 517-518.
[16]Ve Ronique Jubirrmaurin, Agnesrodrigue, Safia Ouahrani bettache, et al. Identification of the nik Gene Cluster of Brucella suis:Regulation and Contribution to Urease Activity. J Bacteriol,2001,183(2):426-434.
[17]Essenberg RC. Sugar metabolism by Brucellae. Vet Microbiol,2002,90: 249-261.
[18]Wu QM, Pei JW, Turse C, et al. Mariner mutagenesis of Brucella melitensis reveals genes with previously uncharacterized roles in virulence and survival. BMC Microbiology,2006,6 (102):147-180.
[19]Gireesh R, Glasner JD, Glover DA, et al. Comparative Whole Genome Hybridization Reveals Genomic Islands in Brucella Species. J Bacteriol,2004, 186(15):5040-5051.
[20]Sreevansan S, Bookout JB, Ringpis F, et al. A multiplex approach to molecular detection of Brucella abortus and/or Mycobacterium bovis infection in cattle. J Clin Microbiol,2000,38(7):2602-2610.
[21]O Kuplulu, B Sarimehmetoglu. Isolation and identification of Brucella spp. in ice cream. Food Control,2004, (15):511-514
[22]Glaser P, M Chandler, E Rocha. Microbial genomics. Res Microbiol,2007, 158(10):721-723.
[23]Ouahrani S, Michaux S, Widada J, et al. Identification and sequence analysis of IS6501, an insertion sequence in Brucella spp.:relationship between genomic structure and the number of IS6501 copies. J Gen Microbiol,1993,139(12): 3265-3273.
[24]Vito G, Del Vecchio, Vinayak Kapatral, et al. The genome of Brucella melitensis. Veterinary Microbiology,2002,90:587-592.
[25]Foster JT, Beckstrom-Sternberg SM, Pearson T, et al. Whole Genome-Based Phylogeny and Divergence of the Genus Brucella. J Bacteriol,2009, (Epub ahead of print)
[26]Wang Y, Chen Z, Qiao F, et al. Comparative proteomics analyses reveal the virB of B. melitensis affects expression of intracellular survival related proteins. PLoS ONE,2009,4(4):e5368.
[27]Morris JA. The use of polyacrylamide gel electrophoresis in taxonomy of Brucella. J Gen Microbiol,1937,6:231-237.
[28]Santos JM. Outer membrane proteins from rough strains of four Brucella species. Infect Immun,1984,46:188-194.
[29]Verstreate DR. Comparison of sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles and antigenic relatedness among outer membrane proteins of 49 Brucella abortus strains. Infect Immun,1984,46:182-187.
[30]Teixeira-Gomes AP. Mapping and identification of Brucella melitensis proteins by two-dimensional electrophoresis and microsequencing. Electrophoresis, 1997,18:156-162.
[31]Teixeira-Gomes AP. Characterization of heat, oxidative and acid stress responses in Brucella melitensis. Infect Immun,2000,68:2954-2961.
[32]Sowa BA. Virulence associated proteins of Brucella abortus identified by paired two-dimensional gel electrophoretic comparisons of virulent, vaccine, and LPS deficient strains. Appl Theor Electrophor,1992,3:33-40.
[33]Wagner MA, Eschenbrenner M, DelVecchio VG, et al. Global analysis of the Brucella melitensis proteome:identification of proteins expressed in laboratory-grown culture. Proteomics,2002,2:1047-1060.
[34]Eschenbrenner M. Comparative proteome analysis of Brucella melitensis vaccine strain Rev land a virulent strain 16M. J Bacteriol,2002,184:4962-4970.
[35]Sowa BA. Virulence associated proteins of Brucella abortus identified by paired two-dimensional gel electrophoretic comparisons of virulent, vaccine, and LPS deficient strains. Appl Theor Electrophor,1992,3:33-40.
[36]Gireesh Rajashekara, Jeremy D Glasner, David A Glover, et al. Comparative Whole-Genome Hybridization Reveals Genomic Islands in Brucella Species. J Bacteriol,2004,186(15):5040-5051.
[37]M Eschenbrenner. Comparative Proteome Analysis of Laboratory Grown Brucella abortus 2308 and Brucella melitensis 16M. J Proteome Res,2006,5(7): 1731-1740.
[38]Lindler LE. Cloning of a Brucella melitensis group 3 antigen gene encoding Omp28, a protein recognized by the humoral immune response during human brucellosis. Infect Immun,1996,64:2490.
[39]Rossetti OL. Cloning of Brucella abortus gene and characterization of expressed 26-kilodalton periplasmic protein:potential use for diagnosis. J Clin Microbiol, 1996,34:165.
[40]赵忠鹏,吴朔,罗德炎.羊种布鲁氏菌疫苗株M5和强毒株16M的比较蛋白质组学研究.中国人兽共患病学报,2007,23(12)：1172-1175.
[41]Cioeckaert A. Classifcation of Brucella spp. isolated from marine mammals by DNA polynorphism at the OMP2 locus. Vet Bull. 1.2002,72(1):20-21.
[42]Linda Eskra, Angie Mathison, Erik Petersen, et al. Brucella:functional genomics and host-pathogen interactions. Animal Health Research Reviews,2007,7(1/2): 1-11.
[43]Meikle PJ, Perry MB, Cherwonogrodzy JW, et al. Fine stucture of A and antigens from Brucel la biovars. Infect Immun,1989,57:2820-2828.
[44]Guerra Humberto. The Brucellae and their success as pathogens. Microbiology, 2007,33(4):325-331.
[45]Anne Tibor, Valerie Wansard, Valery Bielartz. Effect of omplO or ompl9 Deletion on Brucella abortus Outer Membrane Properties and Virulence in Mice Rose-May Delrue. Vet Microbiol,2002,27:257-262.
[46]Seco Mediavilla P, Verger JM, Grayon M, et al. Epitope mapping of the Brucella melitensis BP26 immunogenic protein:usefulness for diagnosis of sheep brucellosis. Clin Diagn Lab Immunol,2003,10(4):647-51.
[47]Debbarh HS, Zygmunt MS. Competitive enzyme-linked immunosorbent assay using monoclonal antibodies to the Brucella melitensis BP26 protein to evaluate antibody responses in infected and B. melitensis Rev.l vaccinated sheep.Vet Microbiol,1996,53(34):325-37.
[48]Cloeckaert A, Jacques I, Grillo MJ, et al. Development and evaluation as vaccines in mice of Brucella melitensis Rev.1 single and double deletion mutants of the bp26 and omp31 genes coding for antigens of diagnostic significance in ovine brucellosis. Vaccine,2004,22(21):2827-35.
[49]Tibor A, Saman E, de Wergifosse P, et al. Molecular characterization occurrence, and immunogenicity in infected sheep and cattle of two minor outer membrane proteins of Brucella abortus. Infect Immun,1996,64(1):100-107.
[50]Thomas A, Ficht, Scott W, et al. A 36-Kilodalton Brucella abortus Cell Envelope Protein is Encoded by Repeated Sequences Closely Linked in the Genomic DNA. Infect Immun,1988,8:2036-2046.
[51]Fischer B. Isolation, renaturation and formation of disulfide bonds of eukaryotic proteins expressed in Escherichia coli as inclusion bodies. Biotechnology and Bioengineering,1993,3(41):9810-9816.
[52]Oliveira SC, Splitter GA. Immunization of mice with recombinant L7/L12 ribosomal protein confers protein confers protection against Brucella abortus infection. Vaccine,1996,14(10):959-962.
[53]Jubier-Maurin V, Boigegrain RA, Cloeckaert A, et al. Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages. Infect Immun, 2001,69(8):4823-30
[54]Matthew D, Edmonds, Cloeckaert A, et al. Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Vet Microbiol,2002,88:205-221
[55]Edmonds MD, Cloeckaert A, Hagius SD, et al. Pathogenicity and protective activityin pregnant goats of a Brucella melitensis Deltaomp25 deletion mutant. Res Vet Sci,2002,72(3):235-239.
[56]Bowden RA, Estein SM, Zygmunt MS, et al. Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies. Microbes Infect,2000,2(5):481-488.
[57]Grillo MJ, Marin CM, Barberan M, et al. Efficacy of bp26 and bp26/omp31 B. melitensis Rev.l deletion mutants against Brucella ovis in rams. Vaccine,2009, 27(2):187-191.
[58]Vizcaino N, Caro Hernandez P, Cloeckaert A, et al. DNA polymorphism in the OMP25/OMP31 family of Brucella spp:identification of a 1.7-kb inversion in Brucella cetaceae and of a 15.1kb genomie island, absent from Brucella ovis, related to the synthesis of smooth lipopolysaccharide. Microbes Infect,2004, 6(9):821-834.
[59]Zhang X, Xu Y, Ling H, et al. Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme. FEBS Lett,1999,458(2):151-156.
[60]Maria Laura Boschiroli, Safia Ouahrani-Bettache, Vincent Foulongne, et al. The Brucella suis virB operon is induced intracellularly in macrophages. PNAS, 2002,99(3):1544-1549.
[61]Felix J Sangari, Jesus Aguero, Juan M Garca-Lobo. The genes for erythritol catabolism are organized as an inducible operon in Brucella abortus. Microbiology,2000,146:487-495.
[62]Tsogtbaatar G, Tachibana M, Watanabe K, et al. Enzyme-linked immunosorbent assay for screening of canine brucellosis using recombinant Cu-Zn superoxide dismutase. J Vet Med Sci,2008,70(12):1387-1389.
[63]Endley S, Mcmurray D, Fiche TA. Interuption of the cydb locus in brucella abortus attenuates ontracellular survival and virulence in the mouse model of infection. Bacteriol,2000,183:2454-2462
[64]Robertson GT, Roop RM. The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice. Mol Microbiol,1999,34:690-700.
[65]Anap Trixeira. Characterization of heat oxidative and stress response in brucella melitensis. Infect Immun,2000,68(5):2954-2961.
[66]Phillip HE, Phillips RW, Kovach ME, et al.Characterization and Genetic Complementation of a Brucella abortus High Temperature-Requirement A (htrA) Deletion Mutant. Infect and Immun,1994,62:4135-4139.
[67]Connolly JP, Comerci D, Alefantis TG, et al. Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development. Proteomics,2006,6(13):3767-3780.
[68]Lin J, TA Ficht. Protein synthesis in brucella abortus induced during macrophage infection. Infect Immun,1995,63:1409-1414.
[69]Endley S, McMurray D, Ficht TA. Interruption of the cydB locus in Brucella abortus attenuates intracellular survival and virulence in the mouse model of infection. J Bacteriol,2001,183(8):2454-2462.
[1]Al Dahouk S, Fleche PL, Nockler K, et al. Evaluation of brucella MLVA typing for human brucellosis. J Microbiol Methods,2007,69:137-145.
[2]Pappas G, Akritidis N, Bosilkovski M, et al. Brucellosis. N Engl J Med,2005,352: 2325-2336.
[3]Hasanjani Roushan MR, Mohrez M, Smailnejad Gangi SM, et al. Epidemiological features and clinical manifestations in 469 adult patients with brucellosis in Northern Iran. Epidemiol Infect,2004,132:1109-1114.
[4]Bandara AB, Poff-Reichow SA, Nikolich M, et al. Simultaneous expression of homologous and heterologous antigens in rough, attenuated Brucella melitensis. Microbes Infect,2009,11(3):424-428.
[5]Kokoglu OF, Hosoglu S, Geyik MF, et al. Clinical and laboratory features of brucellosis in two university hospitals in southeast Turkey. Trop Doct,2006,36: 49-51.
[6]Palanduz A, Palanduz S, Guler K, et al. Brucellosis in a mother and her young infant:probable transmission by breast milk. Int J Infect Dis,2000,4:55-56.
[7]Barroso Espadero D, Arroyo Carrera I, Lopez Rodriguez MJ, et al. The transmission of brucellosis via breast feeding:A report of 2 cases. An Esp Pediatr,1998,48:60-62.
[8]Celebi G, KμLah C, Kilic S, et al. Asymptomatic Brucella bacteraemia and isolation of Brucella melitensis biovar 3 from human breast milk. Scand J Infect Dis,2007,39:205-208.
[9]Al-Kharfy TM. Neonatal brucellosis and blood transfusion:case report and review of the literature. Ann Trop Paediatr,2001,21:349-352.
[10]Doganay M, Aygen B, Esel D. Brucellosis due to blood transfusion. J Hosp Infect 2001,49:151-52.
[11]Cay S, Cagirci G, Maden O, et al. Brucella endocarditis-a registry study. Kardiol Pol,2009,67(3):274-280.
[12]Memish Z, Mah MW, Al Mahmoud S, et al. Brucella bacteraemia:clinical and laboratory observations in 160 patients. J Infect,2000,40:59-63.
[13]Pearce JH, AE Williams, PW Harris-Smith, et al. The chemical basis of the virulent of Brucella abortus. Ⅱ. Erythritol, a constituent of 39 ovine fetal fluids which stimuLates the growth of B. abortus in bovine macrophages. Br J Exp Pathol,1962,43:631.
[14]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[15]Smith H, RB Fritzgeorge. The chemical basis of the virulent of Brucella abortus. V. The basis of intracellular survival and growth in bovine phagocytosis. Br J Exp Pathol,1964,5:174-186.
[16]Mackaness MB. The immunological basis of acquired cellular resistance. J Exp Med,1964,120:105.
[17]Celli J. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med,2003,198:545-556.
[18]Liautard JP. Interactions between professional phagocytes and Brucella spp. Microbiologia,1996,12:197-206.
[19]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[20]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,2:829-835.
[21]Delrue RM. Identification of Brucella spp. genes involved in intracellular trafficking. Cell Microbiol,2001,3:487-497.
[22]Pizarro-Cerda J, Meresse S, Parton RG, et al. Infect Immun,1998,66: 5711-5724.
[23]Gireesh Rajashekara, Linda Eskra, Angie Mathison, et al. Brucella:functional genomics and host-pathogen interactions. Animal Health Research Reviews. 7(1/2):1-11.
[24]Gross A, Spiesser S, Terraza A, et al. Infect Immun,1998,66:1309-1316.
[25]Gross A, Terraza A, Marchant J, et al. J Leukoc Biol,2000,67:335-344.
[26]Kohler S, Foulongne V, Ouahrani-Bettache S, et al. Proc Natl Acad Sci USA, 2002,99:15711-15716.
[27]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[28]Guzman-Verri C. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002, 99:12375-12380
[29]Lamontagne J. Extensive cell envelope modulation is associated with virulence in Brucella abortus. J Proteome Res,2007,6:1519-1529.
[30]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[31]Guzman-Verri C. GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes:direct activation of Cdc42. J Biol Chem,2001,276:44435-44443.
[32]Manterola L. The lipopolysaccharide of Brucella abortus BvrS/BvrR mutants contains lipid A modifications and has higher affinity for bactericidal cationic peptides. J Bacteriol,2005,187:5631-5639.
[33]Liautard JP. Interactions between professional phagocytes and Brucella spp. Microbiologia,1996,12:197-206.
[34]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[35]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,2:829-835.
[36]Delrue RM. Identification of Brucella spp. genes involved in intracellular trafficking. Cell Microbiol,2001,3:487-497.
[37]Keleti G, Feingold DS, Youngner JS. Interferon induction in mice by lipopolysaccharide from Brucella abortus. Infect Immun,1974,10:282-283.
[38]Moreno E, Berman DT, Boettcher LA. Biological activities of Brucella abortus lipopolysaccharides. Infect Immun,1981,31:362-370.
[39]Goldstein J. Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines. Infect Immun,1992,60:1385-1389.
[40]Rasool O. Effect of Brucella abortus lipopolysaccharide on oxidative metabolism and lysozyme release by human neutrophils. Infect Immun,1992,60: 1699-1702.
[41]Riley LK, Robertson DC. Brucellacidal activity of human and bovine polymorphonuclear leukocyte granule extracts against smooth and rough strains of Brucella abortus. Infect Immun,1984,46:231-236.
[42]Lapaque N. Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides. Cell Microbiol,2006,8: 401-413.
[43]Eisenschenk FC, Houle JJ, Hoffmann EM. Mechanism of serum resistance among Brucella abortus isolates. Vet Microbiol,1999,68:235-244.
[44]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[45]Espinosa BJ, Chacaltana J, Mulder M, et al.Comparison of culture techniques at different stages of brucellosis. Am J Trop Med Hyg,2009,80(4):625-627.
[46]Porte F. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect Immun,2003,71:1481-1490
[47]Jimenez de Bagues MR Different responses of macrophages to smooth and rough Brucella spp.:relationship to virulence. Infect Immun,2004,72: 2429-2433.
[48]Baron C, Callaghan D, Lanka, E. Bacterial secrets of secretion:euroco-nfernce on the biology of type IV secretion progressed. Mol Microbiol,2002,43: 1359-1364.
[49]O'Callaghan D, Cazevieille C, Allardet-Servent A, et al. A homologue of the Agroba-cterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretin systems is essential for intracellular survival of Brucella suis. Mol Microbiol, 1999,33:1210-1220.
[50]Carle A, Hoppner C, Ahmed Aly K, et al.The Brucella suis type IV secretion system assembles in the cell envelope of the heterologous host Agrobacterium tumefaciens and increases IncQ plasmid pLSl recipient competence. Infect Immun,2006,74(1):108-117.
[51]Rolan HG, den Hartigh AB, Kahl-McDonagh M, et al.VirB 12 is a serological marker of Brucella infection in experimental and natural hosts. Clin Vaccine Immunol,2008,15(2):208-14
[52]Christie PJ, Vogel JR Bacterial type IV secretion:conjugation systems adapted to delier effectormolecules to host cells. Trends Microbiol,2000,8:354-360
[53]Lai EM, Kado CI. The T-pilus of Agrobacterium tumefaciens. Trends Microbiol, 2000,8:361-369.
[54]Porte F, Liautard JP, Kohler S. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages. Infect Immun,1999,67(8):4041-4047.
[55]F Porte, A Naroeni, S Ouahrani-Bettache, et al. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect Immun,2003,71: 1481-1490.
[56]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,7:829-835.
[57]Naroeni A, Jouy N, Ouahrani-Bettache S, et al. Brucella suis-impaired specific recognition of phagosomes by lysosomes due to phagosomal membrane modi-fications. Infect Immun,2006,9(1):486-493.
[58]Lestrate P, Delrue RM, Danese I, et al. Identification and characterization of in vivo attenuated mutants of Brucella melitensis. Mol Microbiol,2000,38(3): 543-551.
[59]Boschiroli ML, Ouahrani-Bettache S, Foulongne V, et al. Type IV secretion and Brucella virulent. Vet Microbiol,2002,90(1-4):341-348.
[60]Kahl-McDonagh MM, Ficht TA. Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of cleara-nee in BALB/c mice. Infect Immun,2006,74(7):4048-4057.
[61]HG Rolan, RM Tsolis. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect Immun,2007,75: 2965-2973.
[62]CM Roux, HG Rolan, RL Santos, et al. Brucella requires a functional type IV secretion system to elicit innate immune responses in mice, Cell Microbiol, 2007,9:1851-1869.
[63]de Iannino. Osmotic regulation of cyclic 1,2-beta-glucan synthesis. Microbiology, 2000,146:1735-1742.
[64]Briones G. Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells. Infect Immun,2001,69:4528-4535.
[65]Bohin JP Osmoregulated periplasmic glucans in Proteobacteria. FEMS Microbiol Lett,2000,186:11-19.
[66]Arellano-Reynoso B. Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nat Immunol,2005,6:618-625.
[67]SP Salcedo, MI Marchesini, H Lelouard, et al. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btpl. PLoS Pathog, 2008,4:e21.
[68]Conde-Alvarez R. Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Cell Microbiol,2006,8:1322-1335.
[69]Jean-Pierre Gorvel. Brucella:a Mr "Hide" converted into Dr Jekyll. Microbes and Infection,2008,10:1010-1013.
[70]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[71]Elsa I, Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[72]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[73]Gorvel JP. Brucella:a Mr "Hide"converted into Dr Jekyll. Microbes and Infection.2008,10:1010-1013.
[74]Gross A, Terraza A, Ouahrani-Bettache S, et al. In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells, Infect Immun, 2000,68:342-351.
[75]Pei J, Turse JE, Wu Q, et al. Brucella abortus rough mutants induce requires bacterial protein macrophage oncosis that synthesis and direct interaction with the macrophage. Infect Immun,2006,74:2667-26750
[76]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[77]Celli J. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med,2003,198:545-556.
[78]C orbeilL B, KB lauT J, In zanaK H, et al. Killing of Brucella abortus by bovine serum. Infect Immun,1988,56:3251-3261.
[79]Hofmann EM, Houle JJ. Failure of Brucella abortus lipopolysaccharide (LPS) to activate the a It enr ativep athwayo fco mplement.Vet Immunol Immunopathol, 1983,5:65-76.
[80]Femandez-Prada CM. Deletion of who.4 enhances activation of the lectin pathway of complementin Brucella abortus and Brucella melirensis. Infect Immun,2001,69:4407-4416.
[81]Jiang X, Leonard B, Benson R. Macrophage control of Brucella aborms:role of reactive oxygen intermediates and nitricoxide. Cell Immunol,1993,151: 309-319.
[82]Gay B, Sanchez-Tef S, Caravano R. Ultrastructural localization of NADPH-oxidase activity in murine peritoneal macorphages during phagocytosis of Brucella. Correlation with the production of super oxideanions. Virchows Arch B,1984,45:147-155.
[83]Zaitseva MH, Golding J, M anischewitz D, et al. Br ucellaa bortus as apotential vaccine candidate:induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion moleculel surface expression inelutriated human monocytes stimulated heat-inactivated B. abortus.Infect Immun,1996, 64:3109-3117.
[84]Salmeron I M, Rodriguez-Zapata O, Salmeron L, et al. Impaired activity of natural killer cells in patients with acute bruceilosis. Clin Infect Dis,1992,15: 764-770.
[85]ArayaL N, ElzerP H, RoweG E, et al. Temporald evelopment of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J Immunol,1989,143:3330-3337.
[86]Forestier C. Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. J Immunol, 1999,162:6784-6791.
[87]Forestier C. Brucella abortus lipopolysaccharide in murine peritoneal macrophages acts as a down-regulator of T cell activation. J Immunol,2000, 165:5202-5210.
[88]Dash BC, Banerjea AC. Sequence_Specific Cleavage Activities of DNA Enzymes TargetedAgainstHIV_1 Gag andNef Regions. Oligonucleotides,2004, 14(1):41-47.
[89]Ko J, Gendron-Fitzpatrick A, Spliter GA. Susceptibility of interferon regulatory factor (IRF-1) and interferon consensus sequence binding protein (ICSBP) deficient mice to brucellosis. J Immunol,2002,168:2433-2440.
[90]ZhanY, Kelso A, Cheers C. Cytokine production in the murine response to Brucella infection or immunization with antigenic extracts. Immunology,1993, 80:458-464.
[91]Cirl C, Wieser A, Yadav M, et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain containing proteins. Nat Med,2008,14(4):399-406.
[1]Jacob NR, Rodriguez CG, Binaghi MA, et al. Brucellosis complicating chronic non-infectious disorders:diagnostic and therapeutic dilemmas. J Med Microbiol, 2008,57(9):1161-1166.
[2]Corbel MJ. International Committee on Systematic Bacteriology Subcommittee on the taxonomy of Brucella. Int J Syst Bacteriol,1988,38:450-452.
[3]Benkirane A. Ovine and caprine brucellosis:world distribution and control eradication strategies in West Asia/North Africa region. Small Ruminant Research,2006,62:19-25.
[4]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[5]王远志,陈创夫,崔步云,张辉,等.羊种布鲁氏菌生物3型的分离和鉴定.中国预防兽医学报,2007,29(10)：753-756.
[6]王丽.1952-2003年陕西省检出布鲁氏菌特性分析中国地方病学防治杂志,2004,23(6)：576-578.
[7]王鑫,徐彦霞,赵宝珍.羊种布鲁氏菌心内膜炎一例.中华流行病学杂志, 2003,24(4)：303.
[8]梁普伟,张维栋,刘殿礼,等.章丘市布鲁氏菌病疫点的调查及处理.中国地方病防治杂志,2000,15(3)：164.
[9]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[10]ArticlesHawk ET, Greenwood A. The Translational Research Working Group Developmental Pathway for Lifestyle Alterations. Clin Cancer Res,2008,14(18): 5707-5713.
[11]Almeida RA, Oliver SP. Interaction of coagulase-negative Staphylococcus species with bovine mammary epithelial cells. Microbial Pathogenesis,2001, 31(5):205-221.
[12]Elsa I, Castaneda-Roldan, Safia Ouahrani-Bettache, Zeus Saldana, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12): 1877-1887.
[13]Rosa C, del Rocha-Gracia a, Elsa I. Castan [14]Elsa I, Castaneda-Roldan, Fabiola Avelino-F, et al. Adherence of Brucella to human pithelial cells and macrophages is mediated by sialic acid residues. Cellular Microbiology,2004,6(5):435-445.
[15]O Kuplulu, B Sarimehmetoglu. Isolation and identification of Brucella spp. in ice cream. Food Control,2004, (15):511-514.
[16]Cortea A, Scarcelli E, Soares, RM, et al. Detection of Bruclla DNA from aborted bovine fetuses by polymerase chain reaction. Aust Vet J,2001, (79):500-501.
[17]Hawk ET, Greenwood A. The Translational Research Working Group Developmental Pathway for Lifestyle Alterations. Clin Cancer Res,2008,14(18): 5707-13.
[18]张辉,陈创夫,唐莉娟,等.布鲁氏菌病病原快速诊断方法的建立及应用.塔里木大学学报,2008,20(3)：40-43.
[19]崔步云,任泽萍,张秋香,等.山西省2002年128例布病患者流行病学分析.疾病检测,2004,19(6)：216-218.
[20]曾鹏武,李灵,陈胜文.天山马鹿布鲁氏菌病的检疫和防制.中国兽医科技,2004,34(1)：73-75.
[21]莫合塔尔,石保新,韩雄杰,等.塔里木马鹿布氏杆菌病诊断及调查.新疆畜牧业,2002,3：33-34.
[22]Amin A.S, Hamdy ME. Detection of Brucella melitensis in semen using the polymerase chain reaction assay. Vet Microbiol,2001,83:37-44.
[23]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[24]邱昌庆,曹小安,杨春华,等.乳牛布鲁氏菌病DNA快速诊断技术的研究.中国兽医科技,2005,35(2)：85-89.
[25]Diana Sara Leal-Klevezas, Irma O, martinez-Vartinez, et al. Use of Polymerase chain reaction to detect Brucella abortus biovar 1 in infected goats. Veterinary Microbiology,2000, (75):91-97.
[26]丁炜东,曹丽萍,张体银,等.检测新城疫病毒中和抗体的间接ELISA和竞争ELISA方法的初步建立.中国兽医杂志,2005,41(3)：13-15.
[27]张喜悦,王志亮,刘春菊.小反刍兽疫病毒(PPRV)N蛋白的表达与ELISA检测方法的建立.中国兽医学报,2008,28(2)：146-149.
[1]Claire E Dawson, Emma J Stubberfield, Lorraine L Perrett. Phenotypic and molecular characterisation of Brucella isolates from marine mammals. BMC Microbiology,2008,8:224.
[2]Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis,2006,6(9):538-541.
[3]Corbel MJ. International Committee on Systematic Bacteriology Subcommittee on the taxonomy of Brucella. Int J Syst Bacteriol,1988,38:450-452.
[4]Ross HM, Jahans KL, MacMillan AP, et al. Brucella species infection in North Sea seal and cetacean populations. Vet Rec,1996,138:647-648.
[5]Colby LA. The humoral immune response of Elk (Cervus elaphusnelsoni) and mice to vaccination with Brucella abortus strain RB51. Immunol,1997,56-60.
[6]Klaus Nielsen, Robert Duncan DVM. Animal Brucellosis. CRC Press BocaRaton Ann Arbor Boston,1990,478-486.
[7]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[8]Felix J Sangari, Jesus Aguero, Juan M Garca-Lobo. The genes for erythritol catabolism are organized as an inducible operon in Brucella abortus. Microbiology,2000,146:487-495.
[9]Dizon-Townson DS, Lu J Morgan TK, Ward KJ. Genetic expression by fetal chorionic villi during the first trimester of human gestation. Am J Obstet Gynecol, 2000,183(3):706-711.
[10]Meyer ME. Metabolic characterisation of the genus Brucella. VI. Growth stimulation by i-erythritol compared with strain virulence for guinea pigs. J Bacteriol,1967,93:996-1000.
[11]Sperry JF, Robertson DC. Erythritol catabolism by Brucella abortus. J Bacteriol, 1975,121:619-630.
[12]Maria Laura Boschiroli, Safia Ouahrani-Bettache, Vincent Foulongne, et al. The Brucella suis virB operon is induced intracellularly in macrophages. PNAS,2002, 99(3):1544-1549.
[13]Francesca Mariani, Giulia Cappelli, Giovanna Riccardi, et al. Mycobacterium tuberculosis H37Rv comparative gene-expression analysis in synthetic medium and human macrophase. Gene,2000,253:281-291.
[1]DJ Vassallo. The saga of brucellosis:controversy over credit for linking Malta fever with goats milk. The Lancet,1996,348:804-808.
[2]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[3]王远志,陈创夫,崔步云,张辉,等.羊种布鲁氏菌生物3型的分离和鉴定.中国预防兽医学报,2007,29(10)：753-756.
[4]Benkirane A. Ovine and caprine brucellosis:world distribution and control eradication strategies in West Asia/North Africa region. Small Ruminant Research,2006,62:19-25.
[5]莫合塔尔,石保新,韩雄杰,等.塔里木马鹿布氏杆菌病诊断及调查.新疆畜牧业,2002,3：33-34.
[6]曾鹏武,李灵,陈胜文.天山马鹿布鲁氏菌病的检疫和防制.中国兽医科技,2004,34(1)：73-75.
[7]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[8]Elsa I. Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[9]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[10]Klaus Nielsen, Robert Duncan DVM. Animal Brucellosis. CRC Press BocaRaton Ann Arbor Boston,1990.
[11]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[12]Shiverick KT, King A, Frank HG, et al. Cell culture models of human trophoblast II:trophoblast cell lines a workshop report. Placenta,2001,22(SuppIA): S104-S106.
[13]Watarai M, Makino S, Fujii Y, et al. Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication. Cell Microbiol, 2002,4(6):341-355.
[14]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et at. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[15]Linda Eskra, Angela Mathison, Gary Splitter. Microarray Analysis of mRNA Levels from RAW264.7 Macrophages Infected with Brucella abortus. Infect and Immun,2003,71(3):1125-1133.
[1]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[2]Uetz P, Giot L, Cagney G, et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature,2000,403(6770):623-627.
[3]Tong AH, Drees B, Nardelli G, et al. A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science,2002,295(5553):321-324.
[4]Yu M, Wang J, Li W, et al. Proteomic screen defines the hepatocyte nuclear factor 1 alpha-binding partners and identifies HMGB 1 as a new co factor of HNF 1 alpha. Nucleic Acids Res,2008,36(4):1209-1219.
[5]Wu Y, Li Q, Chen XZ. Detecting protein-protein interactions by Far western blotting. Nat Protoc,2007,2(12):3278-84.
[6]Singh CR, Asano K. Localization and characterization of protein-protein interaction sites. Methods Enzymol,2007,429:139-161.
[7]Chang J, Provost P, Taylor JM. Resistance of human hepatitis delta virus RNAs to diceractivity. J Virol,2003,77:11910-11917.
[8]Edmonds MD, Cloeckaert A, Elzer PH. Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Vet Microbiol,2002,88:205-221.
[9]Lin J, Huang S, Zhang Q. Outer membrane proteins:key players for bacterial adaptation in host niches. Microbes Infect,2002,4:325-331.
[10]Jubier Maurin V, Boigegrain RA, Cloeckaert A, et al. Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages. Infect Immun,2001,69: 4823-4830.
[11]Boigegrain RA, Salhi I, Alvarez Martinez MT, et al. Release of periplasmic proteins of Brucella suis upon acidic shock involves the outer membrane protein Omp25. Infect Immun,2004,72:5693-5703.
[112]Weiser JN, Gotschlich EC. Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1. Infect Immun,1991, 59:2252-2258.
[13]Guzman Verri C, Manterola L, Sola-Landa A, et al. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002,99:12375-123800.
[14]尚德秋,李兰玉.布鲁氏菌分子生物学研究现况.中国流行病学杂志,2005,20(5)：272-276.
[15]Edmonds MD, Cloeckaert A, Hagius SD, et al. Pathogenicity and protective activity in pregnant goats of a Brucella melitensis Deltaomp25 deletion mutant. Res Vet Sci,2002,72(3):235-239.
[16]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[17]Elsa I. Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[18]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[19]Gorvel JP. Brucella:a Mr "Hide"converted into Dr Jekyll. Microbes and Infection,2008,10:1010-1013.
[1]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[2]Elsa I, Castaneda-Roldan, Safia Ouahrani-Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[3]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[4]Gorvel JP. Brucella:a Mr "Hide" converted into Dr Jekyll. Microbes and Infection, 2008,10:1010-1013.
[5]Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenothabditls elegans. Nature,1998,391(6669): 808-811.
[6]Tuschl T, Borkhardt A. Small interfering RNAs:a revolutionary tool for the analysis of gene function and gene therapy. Mol Interv,2002,2(3):158-167.
[7]Qin XF, An DS, Chen IS, et al. Inhibition HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA,2003,100(1):183-188.
[8]Radhakrishnan SK, Layden TJ, Carter AL, et al. RNA interference as a new strategy against viral hepatitis. Virology,2004,323(2):173-181.
[9]Kim S, Lee DS, Watanabe K, et al. Interferon-y promotes abortion due to Brucella infection in pregnant mice. BMC Microbiol,2005,5:22.
[10]宋尔卫.RNA干扰的生物学原理与应用.北京,高等教育出版社.2005,47-48.
[11]Qing-Ming Qin, Jianwu Pei, Veronica Ancona, et al. RNAi Screen of Endoplasmic Reticulum-Associated Host Factors Reveals a Role for IRE la in Supporting Brucella Replication. PLoS Pathogens,2008,4(7):1-16.
[12]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[13]Guzman-Verri C. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002,99: 12375-12380.
[14]Lamontagne J. Extensive cell envelope modulation is associated with virulence in Brucella abortus. J Proteome Res,2007,6:1519-1529.
[15]Rossi MS, Fetherston FD, Letoffe S, et al. Identification and characterization of the hemophore-dependent beme acquisition system of Yersinia pestis. Infect Immun,2001,69:6707-6017.
[16]Braun V, Braun M. Active transport iron and siderophore antibiotics. Curr Opin Microbiol,2002,5:194-201.
[17]Dhaenens L, Szczebara F, Husson MO. Identification, characterization and immunogenicity of the lactoferrin binding protein from Helicobacter pylori. Infect Immun,1997,65:514-518.
[18]Denoel PA. Survival of a Bacterioferritin deletion mutant of brucella melitensis 16M in Human Monocyte-Derived Macrophages. Infect immun,1997,65(10): 433-437.
[19]Okuyama T, Tawada T, Furuya H, et al. The role of transferrin and ferritin in the fetal-maternal-placental u-nit. Am J Obstet Gynecol,1985,152:344.
[20]Nunez MT, Glass J, Robinson SH. Mobilization of iron from the plasma membrane of the murine reticulocyte. Biochim Biophys Acta,1978,509:170.
[21]Brown PJ, Johnson PM, Ogbimi AO, et al. Characterization and localization of human placental ferritin. Biochem J,1979,182:763.
[22]Borch-lohnsen B, Hagve TA, Hauge A, et al. Regulation of the iron metabolism. Thorstensen K. Tidsskr Nor Laegeforen,2009,129(9):858-62.
[23]Takami M, Mizumoto K, Kasuya I, et al. Human placental ferritin receptor. Biochim Biophys Acta,1986,884:31.
[24]ZM Qian, HY Li, HZ Sun, et al. Targeted drug delivery via the transferring receptor-mediated endocytosis pathway. Pharmacol Rev,2002,54:561-587.
[25]Bastin J, Drakesmith H, Rees M, et al. Localisation of proteins of iron metabolism in the human placenta and liver. Br J Haematol,2006,134(5): 532-543.
[2]WHO/FAO. The Development of New/Improved Brucellosis Vaccines:Report of WHO Meeting. Geneva Switzerland,1997,1-48.
[3]Cvjetanovic B, Ikic D, Lane WR, et al. Studies of combined quadruple vaccines against diphtheria, pertussis, tetanus, and typhoid fever:reactogenicity and antigenicity. Bull World Health Organ,1972,46(1):47-52.
[4]Ross HM, Jahans KL, MacMillan AP, et al. Brucella species infection in North Sea seal and cetacean populations. Vet Rec,1996,138:647-648.
[5]Claire E Dawson, Emma J Stubberfield, Lorraine L Perrett. Phenotypic and molecular characterisation of Brucella isolates from marine mammals. BMC Microbiology,2008,8:224.
[6]Maquart M, Zygmunt MS, Cloeckaert A. Marine mammal Brucella isolates with different genomic characteristics display a differential response when infecting human macrophages in culture. Microbes Infect,2009,11(3):361-366.
[7]Emilie Fugier, Georgios Pappas, Jean-Pierre Gorvel. Virulence factors in brucellosis:implications for aetiopathogenesis and treatment. Expert Rev Mol Med,2007,9(35):10.1017/S1462399407000543.
[8]刘志文,廖礼维,王莹,等.新疆绵羊种布鲁氏菌的首次分离和鉴定.中国兽医杂志,1983,6：5-7.
[9]张高轩,张银国,刘志文,等.恒河猴人工感染BRUCELLA OVIS后病理学观察及病原回收.中国人兽共患病杂志,1999,15(4)：78-80.
[10]Baldwin CL, AJ Winter. Macrophages and Brucella. Immunol,1994,60:363-80.
[11]Lenntte EH, A Balows, William J, et al. Manual of clinical microbiology. American Society for Microbiology,1985,434-441.
[12]毛开荣.动物布鲁氏菌病防治技术研究进展.中国兽药杂志,2003,(9)：37-40.
[13]Scholz HC, Hubalek Z, Sedlacek I, et al. Brucella microtispnov isolated from the common vole Microtus arvalis. Int J Syst Evol Microbiol,2008,58:375-382.
[14]McDonald WL, Jamaludin R, Mackereth G, et al. Characterization of a Brucella spp. strain as a marine-mammal type despite isolation from apatient with spinal osteomyelitis in New Zealand. J Clin Microbiol,2006,44:4363-4370.
[15]Whatmore AM, Dawson CE, Groussaud P, et al. A marine mammal Brucella genotype associated with zoonotic infection. Emerg Infect Dis,2008,14: 517-518.
[16]Ve Ronique Jubirrmaurin, Agnesrodrigue, Safia Ouahrani bettache, et al. Identification of the nik Gene Cluster of Brucella suis:Regulation and Contribution to Urease Activity. J Bacteriol,2001,183(2):426-434.
[17]Essenberg RC. Sugar metabolism by Brucellae. Vet Microbiol,2002,90: 249-261.
[18]Wu QM, Pei JW, Turse C, et al. Mariner mutagenesis of Brucella melitensis reveals genes with previously uncharacterized roles in virulence and survival. BMC Microbiology,2006,6 (102):147-180.
[19]Gireesh R, Glasner JD, Glover DA, et al. Comparative Whole Genome Hybridization Reveals Genomic Islands in Brucella Species. J Bacteriol,2004, 186(15):5040-5051.
[20]Sreevansan S, Bookout JB, Ringpis F, et al. A multiplex approach to molecular detection of Brucella abortus and/or Mycobacterium bovis infection in cattle. J Clin Microbiol,2000,38(7):2602-2610.
[21]O Kuplulu, B Sarimehmetoglu. Isolation and identification of Brucella spp. in ice cream. Food Control,2004, (15):511-514
[22]Glaser P, M Chandler, E Rocha. Microbial genomics. Res Microbiol,2007, 158(10):721-723.
[23]Ouahrani S, Michaux S, Widada J, et al. Identification and sequence analysis of IS6501, an insertion sequence in Brucella spp.:relationship between genomic structure and the number of IS6501 copies. J Gen Microbiol,1993,139(12): 3265-3273.
[24]Vito G, Del Vecchio, Vinayak Kapatral, et al. The genome of Brucella melitensis. Veterinary Microbiology,2002,90:587-592.
[25]Foster JT, Beckstrom-Sternberg SM, Pearson T, et al. Whole Genome-Based Phylogeny and Divergence of the Genus Brucella. J Bacteriol,2009, (Epub ahead of print)
[26]Wang Y, Chen Z, Qiao F, et al. Comparative proteomics analyses reveal the virB of B. melitensis affects expression of intracellular survival related proteins. PLoS ONE,2009,4(4):e5368.
[27]Morris JA. The use of polyacrylamide gel electrophoresis in taxonomy of Brucella. J Gen Microbiol,1937,6:231-237.
[28]Santos JM. Outer membrane proteins from rough strains of four Brucella species. Infect Immun,1984,46:188-194.
[29]Verstreate DR. Comparison of sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles and antigenic relatedness among outer membrane proteins of 49 Brucella abortus strains. Infect Immun,1984,46:182-187.
[30]Teixeira-Gomes AP. Mapping and identification of Brucella melitensis proteins by two-dimensional electrophoresis and microsequencing. Electrophoresis, 1997,18:156-162.
[31]Teixeira-Gomes AP. Characterization of heat, oxidative and acid stress responses in Brucella melitensis. Infect Immun,2000,68:2954-2961.
[32]Sowa BA. Virulence associated proteins of Brucella abortus identified by paired two-dimensional gel electrophoretic comparisons of virulent, vaccine, and LPS deficient strains. Appl Theor Electrophor,1992,3:33-40.
[33]Wagner MA, Eschenbrenner M, DelVecchio VG, et al. Global analysis of the Brucella melitensis proteome:identification of proteins expressed in laboratory-grown culture. Proteomics,2002,2:1047-1060.
[34]Eschenbrenner M. Comparative proteome analysis of Brucella melitensis vaccine strain Rev land a virulent strain 16M. J Bacteriol,2002,184:4962-4970.
[35]Sowa BA. Virulence associated proteins of Brucella abortus identified by paired two-dimensional gel electrophoretic comparisons of virulent, vaccine, and LPS deficient strains. Appl Theor Electrophor,1992,3:33-40.
[36]Gireesh Rajashekara, Jeremy D Glasner, David A Glover, et al. Comparative Whole-Genome Hybridization Reveals Genomic Islands in Brucella Species. J Bacteriol,2004,186(15):5040-5051.
[37]M Eschenbrenner. Comparative Proteome Analysis of Laboratory Grown Brucella abortus 2308 and Brucella melitensis 16M. J Proteome Res,2006,5(7): 1731-1740.
[38]Lindler LE. Cloning of a Brucella melitensis group 3 antigen gene encoding Omp28, a protein recognized by the humoral immune response during human brucellosis. Infect Immun,1996,64:2490.
[39]Rossetti OL. Cloning of Brucella abortus gene and characterization of expressed 26-kilodalton periplasmic protein:potential use for diagnosis. J Clin Microbiol, 1996,34:165.
[40]赵忠鹏,吴朔,罗德炎.羊种布鲁氏菌疫苗株M5和强毒株16M的比较蛋白质组学研究.中国人兽共患病学报,2007,23(12)：1172-1175.
[41]Cioeckaert A. Classifcation of Brucella spp. isolated from marine mammals by DNA polynorphism at the OMP2 locus. Vet Bull. 1.2002,72(1):20-21.
[42]Linda Eskra, Angie Mathison, Erik Petersen, et al. Brucella:functional genomics and host-pathogen interactions. Animal Health Research Reviews,2007,7(1/2): 1-11.
[43]Meikle PJ, Perry MB, Cherwonogrodzy JW, et al. Fine stucture of A and antigens from Brucel la biovars. Infect Immun,1989,57:2820-2828.
[44]Guerra Humberto. The Brucellae and their success as pathogens. Microbiology, 2007,33(4):325-331.
[45]Anne Tibor, Valerie Wansard, Valery Bielartz. Effect of omplO or ompl9 Deletion on Brucella abortus Outer Membrane Properties and Virulence in Mice Rose-May Delrue. Vet Microbiol,2002,27:257-262.
[46]Seco Mediavilla P, Verger JM, Grayon M, et al. Epitope mapping of the Brucella melitensis BP26 immunogenic protein:usefulness for diagnosis of sheep brucellosis. Clin Diagn Lab Immunol,2003,10(4):647-51.
[47]Debbarh HS, Zygmunt MS. Competitive enzyme-linked immunosorbent assay using monoclonal antibodies to the Brucella melitensis BP26 protein to evaluate antibody responses in infected and B. melitensis Rev.l vaccinated sheep.Vet Microbiol,1996,53(34):325-37.
[48]Cloeckaert A, Jacques I, Grillo MJ, et al. Development and evaluation as vaccines in mice of Brucella melitensis Rev.1 single and double deletion mutants of the bp26 and omp31 genes coding for antigens of diagnostic significance in ovine brucellosis. Vaccine,2004,22(21):2827-35.
[49]Tibor A, Saman E, de Wergifosse P, et al. Molecular characterization occurrence, and immunogenicity in infected sheep and cattle of two minor outer membrane proteins of Brucella abortus. Infect Immun,1996,64(1):100-107.
[50]Thomas A, Ficht, Scott W, et al. A 36-Kilodalton Brucella abortus Cell Envelope Protein is Encoded by Repeated Sequences Closely Linked in the Genomic DNA. Infect Immun,1988,8:2036-2046.
[51]Fischer B. Isolation, renaturation and formation of disulfide bonds of eukaryotic proteins expressed in Escherichia coli as inclusion bodies. Biotechnology and Bioengineering,1993,3(41):9810-9816.
[52]Oliveira SC, Splitter GA. Immunization of mice with recombinant L7/L12 ribosomal protein confers protein confers protection against Brucella abortus infection. Vaccine,1996,14(10):959-962.
[53]Jubier-Maurin V, Boigegrain RA, Cloeckaert A, et al. Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages. Infect Immun, 2001,69(8):4823-30
[54]Matthew D, Edmonds, Cloeckaert A, et al. Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Vet Microbiol,2002,88:205-221
[55]Edmonds MD, Cloeckaert A, Hagius SD, et al. Pathogenicity and protective activityin pregnant goats of a Brucella melitensis Deltaomp25 deletion mutant. Res Vet Sci,2002,72(3):235-239.
[56]Bowden RA, Estein SM, Zygmunt MS, et al. Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies. Microbes Infect,2000,2(5):481-488.
[57]Grillo MJ, Marin CM, Barberan M, et al. Efficacy of bp26 and bp26/omp31 B. melitensis Rev.l deletion mutants against Brucella ovis in rams. Vaccine,2009, 27(2):187-191.
[58]Vizcaino N, Caro Hernandez P, Cloeckaert A, et al. DNA polymorphism in the OMP25/OMP31 family of Brucella spp:identification of a 1.7-kb inversion in Brucella cetaceae and of a 15.1kb genomie island, absent from Brucella ovis, related to the synthesis of smooth lipopolysaccharide. Microbes Infect,2004, 6(9):821-834.
[59]Zhang X, Xu Y, Ling H, et al. Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme. FEBS Lett,1999,458(2):151-156.
[60]Maria Laura Boschiroli, Safia Ouahrani-Bettache, Vincent Foulongne, et al. The Brucella suis virB operon is induced intracellularly in macrophages. PNAS, 2002,99(3):1544-1549.
[61]Felix J Sangari, Jesus Aguero, Juan M Garca-Lobo. The genes for erythritol catabolism are organized as an inducible operon in Brucella abortus. Microbiology,2000,146:487-495.
[62]Tsogtbaatar G, Tachibana M, Watanabe K, et al. Enzyme-linked immunosorbent assay for screening of canine brucellosis using recombinant Cu-Zn superoxide dismutase. J Vet Med Sci,2008,70(12):1387-1389.
[63]Endley S, Mcmurray D, Fiche TA. Interuption of the cydb locus in brucella abortus attenuates ontracellular survival and virulence in the mouse model of infection. Bacteriol,2000,183:2454-2462
[64]Robertson GT, Roop RM. The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice. Mol Microbiol,1999,34:690-700.
[65]Anap Trixeira. Characterization of heat oxidative and stress response in brucella melitensis. Infect Immun,2000,68(5):2954-2961.
[66]Phillip HE, Phillips RW, Kovach ME, et al.Characterization and Genetic Complementation of a Brucella abortus High Temperature-Requirement A (htrA) Deletion Mutant. Infect and Immun,1994,62:4135-4139.
[67]Connolly JP, Comerci D, Alefantis TG, et al. Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development. Proteomics,2006,6(13):3767-3780.
[68]Lin J, TA Ficht. Protein synthesis in brucella abortus induced during macrophage infection. Infect Immun,1995,63:1409-1414.
[69]Endley S, McMurray D, Ficht TA. Interruption of the cydB locus in Brucella abortus attenuates intracellular survival and virulence in the mouse model of infection. J Bacteriol,2001,183(8):2454-2462.
[1]Al Dahouk S, Fleche PL, Nockler K, et al. Evaluation of brucella MLVA typing for human brucellosis. J Microbiol Methods,2007,69:137-145.
[2]Pappas G, Akritidis N, Bosilkovski M, et al. Brucellosis. N Engl J Med,2005,352: 2325-2336.
[3]Hasanjani Roushan MR, Mohrez M, Smailnejad Gangi SM, et al. Epidemiological features and clinical manifestations in 469 adult patients with brucellosis in Northern Iran. Epidemiol Infect,2004,132:1109-1114.
[4]Bandara AB, Poff-Reichow SA, Nikolich M, et al. Simultaneous expression of homologous and heterologous antigens in rough, attenuated Brucella melitensis. Microbes Infect,2009,11(3):424-428.
[5]Kokoglu OF, Hosoglu S, Geyik MF, et al. Clinical and laboratory features of brucellosis in two university hospitals in southeast Turkey. Trop Doct,2006,36: 49-51.
[6]Palanduz A, Palanduz S, Guler K, et al. Brucellosis in a mother and her young infant:probable transmission by breast milk. Int J Infect Dis,2000,4:55-56.
[7]Barroso Espadero D, Arroyo Carrera I, Lopez Rodriguez MJ, et al. The transmission of brucellosis via breast feeding:A report of 2 cases. An Esp Pediatr,1998,48:60-62.
[8]Celebi G, KμLah C, Kilic S, et al. Asymptomatic Brucella bacteraemia and isolation of Brucella melitensis biovar 3 from human breast milk. Scand J Infect Dis,2007,39:205-208.
[9]Al-Kharfy TM. Neonatal brucellosis and blood transfusion:case report and review of the literature. Ann Trop Paediatr,2001,21:349-352.
[10]Doganay M, Aygen B, Esel D. Brucellosis due to blood transfusion. J Hosp Infect 2001,49:151-52.
[11]Cay S, Cagirci G, Maden O, et al. Brucella endocarditis-a registry study. Kardiol Pol,2009,67(3):274-280.
[12]Memish Z, Mah MW, Al Mahmoud S, et al. Brucella bacteraemia:clinical and laboratory observations in 160 patients. J Infect,2000,40:59-63.
[13]Pearce JH, AE Williams, PW Harris-Smith, et al. The chemical basis of the virulent of Brucella abortus. Ⅱ. Erythritol, a constituent of 39 ovine fetal fluids which stimuLates the growth of B. abortus in bovine macrophages. Br J Exp Pathol,1962,43:631.
[14]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[15]Smith H, RB Fritzgeorge. The chemical basis of the virulent of Brucella abortus. V. The basis of intracellular survival and growth in bovine phagocytosis. Br J Exp Pathol,1964,5:174-186.
[16]Mackaness MB. The immunological basis of acquired cellular resistance. J Exp Med,1964,120:105.
[17]Celli J. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med,2003,198:545-556.
[18]Liautard JP. Interactions between professional phagocytes and Brucella spp. Microbiologia,1996,12:197-206.
[19]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[20]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,2:829-835.
[21]Delrue RM. Identification of Brucella spp. genes involved in intracellular trafficking. Cell Microbiol,2001,3:487-497.
[22]Pizarro-Cerda J, Meresse S, Parton RG, et al. Infect Immun,1998,66: 5711-5724.
[23]Gireesh Rajashekara, Linda Eskra, Angie Mathison, et al. Brucella:functional genomics and host-pathogen interactions. Animal Health Research Reviews. 7(1/2):1-11.
[24]Gross A, Spiesser S, Terraza A, et al. Infect Immun,1998,66:1309-1316.
[25]Gross A, Terraza A, Marchant J, et al. J Leukoc Biol,2000,67:335-344.
[26]Kohler S, Foulongne V, Ouahrani-Bettache S, et al. Proc Natl Acad Sci USA, 2002,99:15711-15716.
[27]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[28]Guzman-Verri C. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002, 99:12375-12380
[29]Lamontagne J. Extensive cell envelope modulation is associated with virulence in Brucella abortus. J Proteome Res,2007,6:1519-1529.
[30]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[31]Guzman-Verri C. GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes:direct activation of Cdc42. J Biol Chem,2001,276:44435-44443.
[32]Manterola L. The lipopolysaccharide of Brucella abortus BvrS/BvrR mutants contains lipid A modifications and has higher affinity for bactericidal cationic peptides. J Bacteriol,2005,187:5631-5639.
[33]Liautard JP. Interactions between professional phagocytes and Brucella spp. Microbiologia,1996,12:197-206.
[34]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[35]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,2:829-835.
[36]Delrue RM. Identification of Brucella spp. genes involved in intracellular trafficking. Cell Microbiol,2001,3:487-497.
[37]Keleti G, Feingold DS, Youngner JS. Interferon induction in mice by lipopolysaccharide from Brucella abortus. Infect Immun,1974,10:282-283.
[38]Moreno E, Berman DT, Boettcher LA. Biological activities of Brucella abortus lipopolysaccharides. Infect Immun,1981,31:362-370.
[39]Goldstein J. Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines. Infect Immun,1992,60:1385-1389.
[40]Rasool O. Effect of Brucella abortus lipopolysaccharide on oxidative metabolism and lysozyme release by human neutrophils. Infect Immun,1992,60: 1699-1702.
[41]Riley LK, Robertson DC. Brucellacidal activity of human and bovine polymorphonuclear leukocyte granule extracts against smooth and rough strains of Brucella abortus. Infect Immun,1984,46:231-236.
[42]Lapaque N. Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides. Cell Microbiol,2006,8: 401-413.
[43]Eisenschenk FC, Houle JJ, Hoffmann EM. Mechanism of serum resistance among Brucella abortus isolates. Vet Microbiol,1999,68:235-244.
[44]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[45]Espinosa BJ, Chacaltana J, Mulder M, et al.Comparison of culture techniques at different stages of brucellosis. Am J Trop Med Hyg,2009,80(4):625-627.
[46]Porte F. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect Immun,2003,71:1481-1490
[47]Jimenez de Bagues MR Different responses of macrophages to smooth and rough Brucella spp.:relationship to virulence. Infect Immun,2004,72: 2429-2433.
[48]Baron C, Callaghan D, Lanka, E. Bacterial secrets of secretion:euroco-nfernce on the biology of type IV secretion progressed. Mol Microbiol,2002,43: 1359-1364.
[49]O'Callaghan D, Cazevieille C, Allardet-Servent A, et al. A homologue of the Agroba-cterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretin systems is essential for intracellular survival of Brucella suis. Mol Microbiol, 1999,33:1210-1220.
[50]Carle A, Hoppner C, Ahmed Aly K, et al.The Brucella suis type IV secretion system assembles in the cell envelope of the heterologous host Agrobacterium tumefaciens and increases IncQ plasmid pLSl recipient competence. Infect Immun,2006,74(1):108-117.
[51]Rolan HG, den Hartigh AB, Kahl-McDonagh M, et al.VirB 12 is a serological marker of Brucella infection in experimental and natural hosts. Clin Vaccine Immunol,2008,15(2):208-14
[52]Christie PJ, Vogel JR Bacterial type IV secretion:conjugation systems adapted to delier effectormolecules to host cells. Trends Microbiol,2000,8:354-360
[53]Lai EM, Kado CI. The T-pilus of Agrobacterium tumefaciens. Trends Microbiol, 2000,8:361-369.
[54]Porte F, Liautard JP, Kohler S. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages. Infect Immun,1999,67(8):4041-4047.
[55]F Porte, A Naroeni, S Ouahrani-Bettache, et al. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect Immun,2003,71: 1481-1490.
[56]Pizarro-Cerda J, Moreno E, Gorvel JP. Invasion and intracellular trafficking of Brucella abortus in nonphagocytic cells. Microbes Infect,2000,7:829-835.
[57]Naroeni A, Jouy N, Ouahrani-Bettache S, et al. Brucella suis-impaired specific recognition of phagosomes by lysosomes due to phagosomal membrane modi-fications. Infect Immun,2006,9(1):486-493.
[58]Lestrate P, Delrue RM, Danese I, et al. Identification and characterization of in vivo attenuated mutants of Brucella melitensis. Mol Microbiol,2000,38(3): 543-551.
[59]Boschiroli ML, Ouahrani-Bettache S, Foulongne V, et al. Type IV secretion and Brucella virulent. Vet Microbiol,2002,90(1-4):341-348.
[60]Kahl-McDonagh MM, Ficht TA. Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of cleara-nee in BALB/c mice. Infect Immun,2006,74(7):4048-4057.
[61]HG Rolan, RM Tsolis. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect Immun,2007,75: 2965-2973.
[62]CM Roux, HG Rolan, RL Santos, et al. Brucella requires a functional type IV secretion system to elicit innate immune responses in mice, Cell Microbiol, 2007,9:1851-1869.
[63]de Iannino. Osmotic regulation of cyclic 1,2-beta-glucan synthesis. Microbiology, 2000,146:1735-1742.
[64]Briones G. Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells. Infect Immun,2001,69:4528-4535.
[65]Bohin JP Osmoregulated periplasmic glucans in Proteobacteria. FEMS Microbiol Lett,2000,186:11-19.
[66]Arellano-Reynoso B. Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nat Immunol,2005,6:618-625.
[67]SP Salcedo, MI Marchesini, H Lelouard, et al. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btpl. PLoS Pathog, 2008,4:e21.
[68]Conde-Alvarez R. Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Cell Microbiol,2006,8:1322-1335.
[69]Jean-Pierre Gorvel. Brucella:a Mr "Hide" converted into Dr Jekyll. Microbes and Infection,2008,10:1010-1013.
[70]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[71]Elsa I, Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[72]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[73]Gorvel JP. Brucella:a Mr "Hide"converted into Dr Jekyll. Microbes and Infection.2008,10:1010-1013.
[74]Gross A, Terraza A, Ouahrani-Bettache S, et al. In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells, Infect Immun, 2000,68:342-351.
[75]Pei J, Turse JE, Wu Q, et al. Brucella abortus rough mutants induce requires bacterial protein macrophage oncosis that synthesis and direct interaction with the macrophage. Infect Immun,2006,74:2667-26750
[76]Pizarro-Cerda J. Brucella abortus transits throughthe autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun,1998,66:5711-5724.
[77]Celli J. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med,2003,198:545-556.
[78]C orbeilL B, KB lauT J, In zanaK H, et al. Killing of Brucella abortus by bovine serum. Infect Immun,1988,56:3251-3261.
[79]Hofmann EM, Houle JJ. Failure of Brucella abortus lipopolysaccharide (LPS) to activate the a It enr ativep athwayo fco mplement.Vet Immunol Immunopathol, 1983,5:65-76.
[80]Femandez-Prada CM. Deletion of who.4 enhances activation of the lectin pathway of complementin Brucella abortus and Brucella melirensis. Infect Immun,2001,69:4407-4416.
[81]Jiang X, Leonard B, Benson R. Macrophage control of Brucella aborms:role of reactive oxygen intermediates and nitricoxide. Cell Immunol,1993,151: 309-319.
[82]Gay B, Sanchez-Tef S, Caravano R. Ultrastructural localization of NADPH-oxidase activity in murine peritoneal macorphages during phagocytosis of Brucella. Correlation with the production of super oxideanions. Virchows Arch B,1984,45:147-155.
[83]Zaitseva MH, Golding J, M anischewitz D, et al. Br ucellaa bortus as apotential vaccine candidate:induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion moleculel surface expression inelutriated human monocytes stimulated heat-inactivated B. abortus.Infect Immun,1996, 64:3109-3117.
[84]Salmeron I M, Rodriguez-Zapata O, Salmeron L, et al. Impaired activity of natural killer cells in patients with acute bruceilosis. Clin Infect Dis,1992,15: 764-770.
[85]ArayaL N, ElzerP H, RoweG E, et al. Temporald evelopment of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J Immunol,1989,143:3330-3337.
[86]Forestier C. Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. J Immunol, 1999,162:6784-6791.
[87]Forestier C. Brucella abortus lipopolysaccharide in murine peritoneal macrophages acts as a down-regulator of T cell activation. J Immunol,2000, 165:5202-5210.
[88]Dash BC, Banerjea AC. Sequence_Specific Cleavage Activities of DNA Enzymes TargetedAgainstHIV_1 Gag andNef Regions. Oligonucleotides,2004, 14(1):41-47.
[89]Ko J, Gendron-Fitzpatrick A, Spliter GA. Susceptibility of interferon regulatory factor (IRF-1) and interferon consensus sequence binding protein (ICSBP) deficient mice to brucellosis. J Immunol,2002,168:2433-2440.
[90]ZhanY, Kelso A, Cheers C. Cytokine production in the murine response to Brucella infection or immunization with antigenic extracts. Immunology,1993, 80:458-464.
[91]Cirl C, Wieser A, Yadav M, et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain containing proteins. Nat Med,2008,14(4):399-406.
[1]Jacob NR, Rodriguez CG, Binaghi MA, et al. Brucellosis complicating chronic non-infectious disorders:diagnostic and therapeutic dilemmas. J Med Microbiol, 2008,57(9):1161-1166.
[2]Corbel MJ. International Committee on Systematic Bacteriology Subcommittee on the taxonomy of Brucella. Int J Syst Bacteriol,1988,38:450-452.
[3]Benkirane A. Ovine and caprine brucellosis:world distribution and control eradication strategies in West Asia/North Africa region. Small Ruminant Research,2006,62:19-25.
[4]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[5]王远志,陈创夫,崔步云,张辉,等.羊种布鲁氏菌生物3型的分离和鉴定.中国预防兽医学报,2007,29(10)：753-756.
[6]王丽.1952-2003年陕西省检出布鲁氏菌特性分析中国地方病学防治杂志,2004,23(6)：576-578.
[7]王鑫,徐彦霞,赵宝珍.羊种布鲁氏菌心内膜炎一例.中华流行病学杂志, 2003,24(4)：303.
[8]梁普伟,张维栋,刘殿礼,等.章丘市布鲁氏菌病疫点的调查及处理.中国地方病防治杂志,2000,15(3)：164.
[9]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[10]ArticlesHawk ET, Greenwood A. The Translational Research Working Group Developmental Pathway for Lifestyle Alterations. Clin Cancer Res,2008,14(18): 5707-5713.
[11]Almeida RA, Oliver SP. Interaction of coagulase-negative Staphylococcus species with bovine mammary epithelial cells. Microbial Pathogenesis,2001, 31(5):205-221.
[12]Elsa I, Castaneda-Roldan, Safia Ouahrani-Bettache, Zeus Saldana, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12): 1877-1887.
[13]Rosa C, del Rocha-Gracia a, Elsa I. Castan
[15]O Kuplulu, B Sarimehmetoglu. Isolation and identification of Brucella spp. in ice cream. Food Control,2004, (15):511-514.
[16]Cortea A, Scarcelli E, Soares, RM, et al. Detection of Bruclla DNA from aborted bovine fetuses by polymerase chain reaction. Aust Vet J,2001, (79):500-501.
[17]Hawk ET, Greenwood A. The Translational Research Working Group Developmental Pathway for Lifestyle Alterations. Clin Cancer Res,2008,14(18): 5707-13.
[18]张辉,陈创夫,唐莉娟,等.布鲁氏菌病病原快速诊断方法的建立及应用.塔里木大学学报,2008,20(3)：40-43.
[19]崔步云,任泽萍,张秋香,等.山西省2002年128例布病患者流行病学分析.疾病检测,2004,19(6)：216-218.
[20]曾鹏武,李灵,陈胜文.天山马鹿布鲁氏菌病的检疫和防制.中国兽医科技,2004,34(1)：73-75.
[21]莫合塔尔,石保新,韩雄杰,等.塔里木马鹿布氏杆菌病诊断及调查.新疆畜牧业,2002,3：33-34.
[22]Amin A.S, Hamdy ME. Detection of Brucella melitensis in semen using the polymerase chain reaction assay. Vet Microbiol,2001,83:37-44.
[23]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[24]邱昌庆,曹小安,杨春华,等.乳牛布鲁氏菌病DNA快速诊断技术的研究.中国兽医科技,2005,35(2)：85-89.
[25]Diana Sara Leal-Klevezas, Irma O, martinez-Vartinez, et al. Use of Polymerase chain reaction to detect Brucella abortus biovar 1 in infected goats. Veterinary Microbiology,2000, (75):91-97.
[26]丁炜东,曹丽萍,张体银,等.检测新城疫病毒中和抗体的间接ELISA和竞争ELISA方法的初步建立.中国兽医杂志,2005,41(3)：13-15.
[27]张喜悦,王志亮,刘春菊.小反刍兽疫病毒(PPRV)N蛋白的表达与ELISA检测方法的建立.中国兽医学报,2008,28(2)：146-149.
[1]Claire E Dawson, Emma J Stubberfield, Lorraine L Perrett. Phenotypic and molecular characterisation of Brucella isolates from marine mammals. BMC Microbiology,2008,8:224.
[2]Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis,2006,6(9):538-541.
[3]Corbel MJ. International Committee on Systematic Bacteriology Subcommittee on the taxonomy of Brucella. Int J Syst Bacteriol,1988,38:450-452.
[4]Ross HM, Jahans KL, MacMillan AP, et al. Brucella species infection in North Sea seal and cetacean populations. Vet Rec,1996,138:647-648.
[5]Colby LA. The humoral immune response of Elk (Cervus elaphusnelsoni) and mice to vaccination with Brucella abortus strain RB51. Immunol,1997,56-60.
[6]Klaus Nielsen, Robert Duncan DVM. Animal Brucellosis. CRC Press BocaRaton Ann Arbor Boston,1990,478-486.
[7]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[8]Felix J Sangari, Jesus Aguero, Juan M Garca-Lobo. The genes for erythritol catabolism are organized as an inducible operon in Brucella abortus. Microbiology,2000,146:487-495.
[9]Dizon-Townson DS, Lu J Morgan TK, Ward KJ. Genetic expression by fetal chorionic villi during the first trimester of human gestation. Am J Obstet Gynecol, 2000,183(3):706-711.
[10]Meyer ME. Metabolic characterisation of the genus Brucella. VI. Growth stimulation by i-erythritol compared with strain virulence for guinea pigs. J Bacteriol,1967,93:996-1000.
[11]Sperry JF, Robertson DC. Erythritol catabolism by Brucella abortus. J Bacteriol, 1975,121:619-630.
[12]Maria Laura Boschiroli, Safia Ouahrani-Bettache, Vincent Foulongne, et al. The Brucella suis virB operon is induced intracellularly in macrophages. PNAS,2002, 99(3):1544-1549.
[13]Francesca Mariani, Giulia Cappelli, Giovanna Riccardi, et al. Mycobacterium tuberculosis H37Rv comparative gene-expression analysis in synthetic medium and human macrophase. Gene,2000,253:281-291.
[1]DJ Vassallo. The saga of brucellosis:controversy over credit for linking Malta fever with goats milk. The Lancet,1996,348:804-808.
[2]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[3]王远志,陈创夫,崔步云,张辉,等.羊种布鲁氏菌生物3型的分离和鉴定.中国预防兽医学报,2007,29(10)：753-756.
[4]Benkirane A. Ovine and caprine brucellosis:world distribution and control eradication strategies in West Asia/North Africa region. Small Ruminant Research,2006,62:19-25.
[5]莫合塔尔,石保新,韩雄杰,等.塔里木马鹿布氏杆菌病诊断及调查.新疆畜牧业,2002,3：33-34.
[6]曾鹏武,李灵,陈胜文.天山马鹿布鲁氏菌病的检疫和防制.中国兽医科技,2004,34(1)：73-75.
[7]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[8]Elsa I. Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[9]Keppie J, AE Williams, K Witt, et al. The role of erythritol in the tissue localization of the Brucellae. Br J Exp Pathol,1965,46:104.
[10]Klaus Nielsen, Robert Duncan DVM. Animal Brucellosis. CRC Press BocaRaton Ann Arbor Boston,1990.
[11]尚德秋.中国布鲁氏菌病防治科研50年.中华流行病学杂志,2000,21(1)：55-57.
[12]Shiverick KT, King A, Frank HG, et al. Cell culture models of human trophoblast II:trophoblast cell lines a workshop report. Placenta,2001,22(SuppIA): S104-S106.
[13]Watarai M, Makino S, Fujii Y, et al. Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication. Cell Microbiol, 2002,4(6):341-355.
[14]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et at. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[15]Linda Eskra, Angela Mathison, Gary Splitter. Microarray Analysis of mRNA Levels from RAW264.7 Macrophages Infected with Brucella abortus. Infect and Immun,2003,71(3):1125-1133.
[1]卫疾控发(2007)286号.卫生部、农业部关于加强布鲁氏菌病防治工作的通知.卫生部公报,2008,1：33-34.
[2]Uetz P, Giot L, Cagney G, et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature,2000,403(6770):623-627.
[3]Tong AH, Drees B, Nardelli G, et al. A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science,2002,295(5553):321-324.
[4]Yu M, Wang J, Li W, et al. Proteomic screen defines the hepatocyte nuclear factor 1 alpha-binding partners and identifies HMGB 1 as a new co factor of HNF 1 alpha. Nucleic Acids Res,2008,36(4):1209-1219.
[5]Wu Y, Li Q, Chen XZ. Detecting protein-protein interactions by Far western blotting. Nat Protoc,2007,2(12):3278-84.
[6]Singh CR, Asano K. Localization and characterization of protein-protein interaction sites. Methods Enzymol,2007,429:139-161.
[7]Chang J, Provost P, Taylor JM. Resistance of human hepatitis delta virus RNAs to diceractivity. J Virol,2003,77:11910-11917.
[8]Edmonds MD, Cloeckaert A, Elzer PH. Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Vet Microbiol,2002,88:205-221.
[9]Lin J, Huang S, Zhang Q. Outer membrane proteins:key players for bacterial adaptation in host niches. Microbes Infect,2002,4:325-331.
[10]Jubier Maurin V, Boigegrain RA, Cloeckaert A, et al. Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages. Infect Immun,2001,69: 4823-4830.
[11]Boigegrain RA, Salhi I, Alvarez Martinez MT, et al. Release of periplasmic proteins of Brucella suis upon acidic shock involves the outer membrane protein Omp25. Infect Immun,2004,72:5693-5703.
[112]Weiser JN, Gotschlich EC. Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1. Infect Immun,1991, 59:2252-2258.
[13]Guzman Verri C, Manterola L, Sola-Landa A, et al. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002,99:12375-123800.
[14]尚德秋,李兰玉.布鲁氏菌分子生物学研究现况.中国流行病学杂志,2005,20(5)：272-276.
[15]Edmonds MD, Cloeckaert A, Hagius SD, et al. Pathogenicity and protective activity in pregnant goats of a Brucella melitensis Deltaomp25 deletion mutant. Res Vet Sci,2002,72(3):235-239.
[16]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[17]Elsa I. Castaneda-Roldan, Safia Ouahrani Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[18]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[19]Gorvel JP. Brucella:a Mr "Hide"converted into Dr Jekyll. Microbes and Infection,2008,10:1010-1013.
[1]Suk Kima, Masahisa Wataraia, Hiroshi Suzuki, et al. Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathogenesis,2004,37:11-19.
[2]Elsa I, Castaneda-Roldan, Safia Ouahrani-Bettache, et al. Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells. Cellular Microbiology,2006,8(12):1877-1887.
[3]Kenta Watanabe, Masato Tachibana, Satoshi Tanaka, et al. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion. BMC Microbiology,2008,8:1-12.
[4]Gorvel JP. Brucella:a Mr "Hide" converted into Dr Jekyll. Microbes and Infection, 2008,10:1010-1013.
[5]Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenothabditls elegans. Nature,1998,391(6669): 808-811.
[6]Tuschl T, Borkhardt A. Small interfering RNAs:a revolutionary tool for the analysis of gene function and gene therapy. Mol Interv,2002,2(3):158-167.
[7]Qin XF, An DS, Chen IS, et al. Inhibition HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA,2003,100(1):183-188.
[8]Radhakrishnan SK, Layden TJ, Carter AL, et al. RNA interference as a new strategy against viral hepatitis. Virology,2004,323(2):173-181.
[9]Kim S, Lee DS, Watanabe K, et al. Interferon-y promotes abortion due to Brucella infection in pregnant mice. BMC Microbiol,2005,5:22.
[10]宋尔卫.RNA干扰的生物学原理与应用.北京,高等教育出版社.2005,47-48.
[11]Qing-Ming Qin, Jianwu Pei, Veronica Ancona, et al. RNAi Screen of Endoplasmic Reticulum-Associated Host Factors Reveals a Role for IRE la in Supporting Brucella Replication. PLoS Pathogens,2008,4(7):1-16.
[12]Sola-Landa A. A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol Microbiol,1998,29:125-138.
[13]Guzman-Verri C. The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae. Proc Natl Acad Sci USA,2002,99: 12375-12380.
[14]Lamontagne J. Extensive cell envelope modulation is associated with virulence in Brucella abortus. J Proteome Res,2007,6:1519-1529.
[15]Rossi MS, Fetherston FD, Letoffe S, et al. Identification and characterization of the hemophore-dependent beme acquisition system of Yersinia pestis. Infect Immun,2001,69:6707-6017.
[16]Braun V, Braun M. Active transport iron and siderophore antibiotics. Curr Opin Microbiol,2002,5:194-201.
[17]Dhaenens L, Szczebara F, Husson MO. Identification, characterization and immunogenicity of the lactoferrin binding protein from Helicobacter pylori. Infect Immun,1997,65:514-518.
[18]Denoel PA. Survival of a Bacterioferritin deletion mutant of brucella melitensis 16M in Human Monocyte-Derived Macrophages. Infect immun,1997,65(10): 433-437.
[19]Okuyama T, Tawada T, Furuya H, et al. The role of transferrin and ferritin in the fetal-maternal-placental u-nit. Am J Obstet Gynecol,1985,152:344.
[20]Nunez MT, Glass J, Robinson SH. Mobilization of iron from the plasma membrane of the murine reticulocyte. Biochim Biophys Acta,1978,509:170.
[21]Brown PJ, Johnson PM, Ogbimi AO, et al. Characterization and localization of human placental ferritin. Biochem J,1979,182:763.
[22]Borch-lohnsen B, Hagve TA, Hauge A, et al. Regulation of the iron metabolism. Thorstensen K. Tidsskr Nor Laegeforen,2009,129(9):858-62.
[23]Takami M, Mizumoto K, Kasuya I, et al. Human placental ferritin receptor. Biochim Biophys Acta,1986,884:31.
[24]ZM Qian, HY Li, HZ Sun, et al. Targeted drug delivery via the transferring receptor-mediated endocytosis pathway. Pharmacol Rev,2002,54:561-587.
[25]Bastin J, Drakesmith H, Rees M, et al. Localisation of proteins of iron metabolism in the human placenta and liver. Br J Haematol,2006,134(5): 532-543.
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