羊布鲁氏菌蛋白质组学分析及免疫候选抗原的筛选与鉴定
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摘要
布鲁氏菌病(简称布病)是由布鲁氏菌引起的一种人兽共患的传染病,是重要的人畜共患病,在世界各地都有广泛流行,尤其是在发展中国家。该病自1887年Bruce发现羊布鲁氏菌以来呈现了复发的趋势,布病的地理分布在不断的改变,新的疫源地不断涌现,数据显示全世界因布病在动物产品以及公共卫生方面的经济损失是巨大的。
当前控制和根除布病最关键的问题在于其致病机制不完全清楚以及没有安全有效的疫苗。布鲁氏菌属于胞内寄生菌,其强毒株和疫苗株的外膜结构存在着很大的差异,进而导致它们的胞内寄生过程存在着明显的差异。为此,本研究利用比较蛋白质组学技术对羊布鲁氏菌强毒株16M和疫苗株M5的外膜蛋白进行了比较分析研究,并用半定量RT-PCR技术对这些差异蛋白进行转录水平的分析,从而了解了布鲁氏菌两个不同毒力菌株外膜蛋白的差异表达情况。通过生物信息学数据检索和相关文献数据查询,对这些差异蛋白在细菌生命活动中所发挥的生物学作用以及亚细胞定位等相关信息进行分析,以此来阐释它们与布鲁氏菌的致弱机制、毒力以及胞内寄生等过程中发挥的重要作用。
在布病高发地区,所有易感动物的免疫和感染动物的根除是防控布病唯一手段。目前使用的疫苗仍然是以畜用减毒活疫苗为主,如S19,Rev.1,M5,S2等,但他们在安全性和有效性方面存在很多问题,比如容易引起人的感染,干扰血清学诊断,免疫后引起孕畜流产以及毒株扩增等缺点。至今还没有一种安全、有效的人用布病疫苗。然而能克服上述缺点的新型疫苗的研制如亚单位疫苗等备受青睐,成为了当前控制人畜布病的迫切需求。
本研究利用免疫蛋白质组学技术在羊布鲁氏菌16M全菌蛋白中进行了免疫候选抗原的筛选鉴定,结合分子生物学和疫苗学验证了其免疫功能,以打破布病新型疫苗研制的瓶颈,为布病防治提供新的依据。
首先,利用免疫蛋白质组学技术,对羊布鲁氏菌强毒株16M全细胞蛋白进行了提取并进行双向电泳分离,用临床上采集到的自然感染布鲁氏菌的人,牛羊的布病血清进行Western-blotting分析,从中获得了被三种血清共同识别的免疫候选抗原,即共同抗原。这些蛋白的发现为研制布鲁氏菌亚单位疫苗提供了候选抗原。
其次,为了进一步验证这些免疫候选抗原的免疫原性和免疫保护能力,我们对这些蛋白进行了原核表达,并在小鼠体内进行了免疫原性和免疫保护能力的评价,进一步为筛选确实有效的布鲁氏菌亚单位疫苗候选抗原奠定基础。
通过以上实验研究,我们得到了如下结果：
1.羊布鲁氏菌强毒株16M和弱毒株M5的膜蛋白比较蛋白质组学结果显示,一共有33个差异蛋白点,经质谱鉴定和生物学信息检索后发现它们代表了26个开放阅读框。其中有22种蛋白在布鲁氏菌强毒株16M上高表达,4种蛋白在疫苗株M5上高表达。通过生物信息学数据检索以及相关文献数据显示,在强毒株内高表达的蛋白在布鲁氏菌的能量代谢,脂肪代谢,蛋白质及氨基酸的合成以及细菌外膜多糖的合成等生物过程中发挥着重要作用。同时在M5株中高表达的蛋白是细菌的重要免疫原性蛋白。半定量RT-PCR结果也显示了部分蛋白在转录水平上也存在着差异,如wbkC (spot16), UTP-glucose-1-hosphate-ridylyltransferase spot 35), purH (spot 20), Omp10 (spot 33), sucB (spot 27)。这些差异蛋白的发现将为我们解释布鲁氏菌的致弱机制提供了线索,同时也获得了一些与毒力和免疫相关的分子。
2.羊布鲁氏菌标准毒株16M全细胞蛋白免疫蛋白组学结果显示,利用布鲁氏菌感染的人、牛、羊血清,筛选出56种免疫候选蛋白,其中有11种蛋白是三种血清共同识别的抗原。
3.候选抗原的原核表达结果显示,7种蛋白被成功表达。辅以佐剂免疫小鼠,体液免疫、细胞免疫以及攻毒保护性实验结果显示,7种候选抗原中有4种候选抗原,即蛋白ahcY (spot 5), RSβ(spot 6), RSα(spot 12)和Isovaleryl-CoA dehydrogenase (spot 17),能够诱导高水平IL-2和IFN-γ为特征的Th1型细胞免疫反应,并能够抗羊布鲁氏菌毒力株16M的攻毒,提供的保护力分别为2.13,1.12,1.12和1.24。其中蛋白ahcY提供的保护力(2.13)与疫苗株M5提供的保护力相当(2.34)。
总之,本研究为揭示布鲁氏菌致弱机制,分析外膜蛋白在布鲁氏菌胞内寄生以及毒力等方面发挥的作用提供了依据。同时我们的方法结合了免疫蛋白组学技术和免疫候选抗原的免疫原性和保护能力的评价方法,为布病亚单位疫苗候选抗原的筛选提供了新的策略。
Brucellosis, which is caused by Brucella, is one of the most important bacterial zoonoses endemic in many countries, especially in developing countries. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Bruce in 1887. The geographical distribution of brucellosis is constantly changing, with new foci emerging or re-emerging. All data suggest that worldwide economic losses due to brucellosis are extensive not only in animal production but also in public health.
The most critical problem that controlling and eradicating brucellosis in animals and human beings is that the investigation in its pathogenic mechanism is not fully clear and have no safe and effective brucellosis vaccines. Brucella is an intracellular bacterium.and the intracellular survival mechanism of the virulent strains are completely different from the vaccine ones, which maybe caused by the different structure in their outer membranes.Therefore, in the present study,the outer membrane proteins of the two strains were analyzed by comparative proteomitics, and these different expressed proteins were further analyzed in transcriptional level by the semiquantitative RT-PCR, and the related outer membranes were identified, which provide new clues for the understanding on the role of outer membrane proteins in Brucella virulence and intracellular survival.
In regions with high prevalence of the disease, the only way of controlling and eradicating this zoonosis is by vaccination of all susceptible hosts and elimination of infected animals. They remains used to vaccinate the animals, although live, attenuated vaccine, such as S19,Rev.1,M5,S2 have some disadvantages:they can be infectious for humans; they can interfere with diagnosis; they may result in abortions when administered to pregnant animals; and the vaccine strain can spread in the region. Howerver, have no a safe and effective vaccine against human brucellosis. It will be favor that a new vaccine overcoming the above-mentioned drawback,such as subunit vaccine, which will be urgent needs for controlling the brucellosis in animals and humans.
In the present study, the immunogenic candidate antigens were identified by immoproteomics from B.melitensis 16M soluble proteins. And tne immunologic function were further evaluated by combining the molecular biology and vaccinology with the aim to design new-type vaccines against Brucella.
First, the immoproteomics strategy was used to screen novel immunogenic candidate proteins for the development of brucellosis subunit vaccine.The soluble proteins of Brucella melitensis were extracted and separated by two-dimensional electrophoresis (2-DE), and the Western blotting analysis were performed probing with the Brucella-infected serm from humans, cattles and goats.The immunodominant proteins were identified by Liquid chromatography tandem mass spectrometry (LC-MS/MS).Some common immunodominant proteins recognized by the three different serum will be new immunogenic candidate proteins for the development of brucellosis subunit vaccine.
Then, these immunogenic candidate proteins were expressed in E.coli for evaluating their immunogenicity and protective ability in the mice model, which laid a foundation for obtaining really effective vaccine antigens candidates.
The corresponding results were obtained based on the above studies:
1、33 differentially expressed proteins from Brucella melitensis virulent strain 16M and vaccine strain M5 outer membrane proteins were found.The results of LC-MS/MS and bioinfermatics indicated that they represented 26 open reading frames. And 22 and 5 proteins were up-regulated in 16M and M5, respectively. The data of bioinfermation retrieval and related references showed that the up-regulated proteins in 16M mainly participated in energy metabolism, fat metabolism, protein, amino acid and polysaccharides biosynthesis and the one in M5 were important immunogenic proteins.The results of semi-quantitative RT-PCR showed that 5 Brucella memebrane proteins, which are wbkC (piont16), UTP-glucose-1-phosphate-uridylyltransferase (piont 35), purH (piont 20), Omp10 (piont 33) and sucB (piont 27), are also difference in transcription level, which basically participate in bacteria cell membrane biosynthesis.
2、The 56 immunodominant proteins were successfully identified by LC-MS/MS. Among them,11 common antigens were recognized by the serum from Brucella-infected humans, cattles and goats serum.
3、The results from the evaluation of immunogenicity and protective ablity in mice model showed that 4 of 11 immunodominant proteins, they are ahcY(piont 5), RSβ(piont 6), RSα(piont 12), Isovaleryl-CoA dehydrogenase (piont 17), could significantly induce the Th1 cell immnune response characterized by high level of IFN-γand IL-2. And they provided partially protective ability against B.melitensis 16M chanllenge, They provided the log unit protection of 2.13,1.12,1.12 and 1.24, respectively.And the protein ahcY can confer the similar profective ability(2.13) to the vaccine strain M5 (2.34).
Finally, our study provided the basis to reveal that the role of Brucella membrane protein in Brucella virulence and intracellular survival and our approaches may provide a new strategy for screening vaccine candidates in combination with immunoproteomics and analysis of the immunogenicity and protective ability in a mouse model.
当前控制和根除布病最关键的问题在于其致病机制不完全清楚以及没有安全有效的疫苗。布鲁氏菌属于胞内寄生菌,其强毒株和疫苗株的外膜结构存在着很大的差异,进而导致它们的胞内寄生过程存在着明显的差异。为此,本研究利用比较蛋白质组学技术对羊布鲁氏菌强毒株16M和疫苗株M5的外膜蛋白进行了比较分析研究,并用半定量RT-PCR技术对这些差异蛋白进行转录水平的分析,从而了解了布鲁氏菌两个不同毒力菌株外膜蛋白的差异表达情况。通过生物信息学数据检索和相关文献数据查询,对这些差异蛋白在细菌生命活动中所发挥的生物学作用以及亚细胞定位等相关信息进行分析,以此来阐释它们与布鲁氏菌的致弱机制、毒力以及胞内寄生等过程中发挥的重要作用。
在布病高发地区,所有易感动物的免疫和感染动物的根除是防控布病唯一手段。目前使用的疫苗仍然是以畜用减毒活疫苗为主,如S19,Rev.1,M5,S2等,但他们在安全性和有效性方面存在很多问题,比如容易引起人的感染,干扰血清学诊断,免疫后引起孕畜流产以及毒株扩增等缺点。至今还没有一种安全、有效的人用布病疫苗。然而能克服上述缺点的新型疫苗的研制如亚单位疫苗等备受青睐,成为了当前控制人畜布病的迫切需求。
本研究利用免疫蛋白质组学技术在羊布鲁氏菌16M全菌蛋白中进行了免疫候选抗原的筛选鉴定,结合分子生物学和疫苗学验证了其免疫功能,以打破布病新型疫苗研制的瓶颈,为布病防治提供新的依据。
首先,利用免疫蛋白质组学技术,对羊布鲁氏菌强毒株16M全细胞蛋白进行了提取并进行双向电泳分离,用临床上采集到的自然感染布鲁氏菌的人,牛羊的布病血清进行Western-blotting分析,从中获得了被三种血清共同识别的免疫候选抗原,即共同抗原。这些蛋白的发现为研制布鲁氏菌亚单位疫苗提供了候选抗原。
其次,为了进一步验证这些免疫候选抗原的免疫原性和免疫保护能力,我们对这些蛋白进行了原核表达,并在小鼠体内进行了免疫原性和免疫保护能力的评价,进一步为筛选确实有效的布鲁氏菌亚单位疫苗候选抗原奠定基础。
通过以上实验研究,我们得到了如下结果：
1.羊布鲁氏菌强毒株16M和弱毒株M5的膜蛋白比较蛋白质组学结果显示,一共有33个差异蛋白点,经质谱鉴定和生物学信息检索后发现它们代表了26个开放阅读框。其中有22种蛋白在布鲁氏菌强毒株16M上高表达,4种蛋白在疫苗株M5上高表达。通过生物信息学数据检索以及相关文献数据显示,在强毒株内高表达的蛋白在布鲁氏菌的能量代谢,脂肪代谢,蛋白质及氨基酸的合成以及细菌外膜多糖的合成等生物过程中发挥着重要作用。同时在M5株中高表达的蛋白是细菌的重要免疫原性蛋白。半定量RT-PCR结果也显示了部分蛋白在转录水平上也存在着差异,如wbkC (spot16), UTP-glucose-1-hosphate-ridylyltransferase spot 35), purH (spot 20), Omp10 (spot 33), sucB (spot 27)。这些差异蛋白的发现将为我们解释布鲁氏菌的致弱机制提供了线索,同时也获得了一些与毒力和免疫相关的分子。
2.羊布鲁氏菌标准毒株16M全细胞蛋白免疫蛋白组学结果显示,利用布鲁氏菌感染的人、牛、羊血清,筛选出56种免疫候选蛋白,其中有11种蛋白是三种血清共同识别的抗原。
3.候选抗原的原核表达结果显示,7种蛋白被成功表达。辅以佐剂免疫小鼠,体液免疫、细胞免疫以及攻毒保护性实验结果显示,7种候选抗原中有4种候选抗原,即蛋白ahcY (spot 5), RSβ(spot 6), RSα(spot 12)和Isovaleryl-CoA dehydrogenase (spot 17),能够诱导高水平IL-2和IFN-γ为特征的Th1型细胞免疫反应,并能够抗羊布鲁氏菌毒力株16M的攻毒,提供的保护力分别为2.13,1.12,1.12和1.24。其中蛋白ahcY提供的保护力(2.13)与疫苗株M5提供的保护力相当(2.34)。
总之,本研究为揭示布鲁氏菌致弱机制,分析外膜蛋白在布鲁氏菌胞内寄生以及毒力等方面发挥的作用提供了依据。同时我们的方法结合了免疫蛋白组学技术和免疫候选抗原的免疫原性和保护能力的评价方法,为布病亚单位疫苗候选抗原的筛选提供了新的策略。
Brucellosis, which is caused by Brucella, is one of the most important bacterial zoonoses endemic in many countries, especially in developing countries. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Bruce in 1887. The geographical distribution of brucellosis is constantly changing, with new foci emerging or re-emerging. All data suggest that worldwide economic losses due to brucellosis are extensive not only in animal production but also in public health.
The most critical problem that controlling and eradicating brucellosis in animals and human beings is that the investigation in its pathogenic mechanism is not fully clear and have no safe and effective brucellosis vaccines. Brucella is an intracellular bacterium.and the intracellular survival mechanism of the virulent strains are completely different from the vaccine ones, which maybe caused by the different structure in their outer membranes.Therefore, in the present study,the outer membrane proteins of the two strains were analyzed by comparative proteomitics, and these different expressed proteins were further analyzed in transcriptional level by the semiquantitative RT-PCR, and the related outer membranes were identified, which provide new clues for the understanding on the role of outer membrane proteins in Brucella virulence and intracellular survival.
In regions with high prevalence of the disease, the only way of controlling and eradicating this zoonosis is by vaccination of all susceptible hosts and elimination of infected animals. They remains used to vaccinate the animals, although live, attenuated vaccine, such as S19,Rev.1,M5,S2 have some disadvantages:they can be infectious for humans; they can interfere with diagnosis; they may result in abortions when administered to pregnant animals; and the vaccine strain can spread in the region. Howerver, have no a safe and effective vaccine against human brucellosis. It will be favor that a new vaccine overcoming the above-mentioned drawback,such as subunit vaccine, which will be urgent needs for controlling the brucellosis in animals and humans.
In the present study, the immunogenic candidate antigens were identified by immoproteomics from B.melitensis 16M soluble proteins. And tne immunologic function were further evaluated by combining the molecular biology and vaccinology with the aim to design new-type vaccines against Brucella.
First, the immoproteomics strategy was used to screen novel immunogenic candidate proteins for the development of brucellosis subunit vaccine.The soluble proteins of Brucella melitensis were extracted and separated by two-dimensional electrophoresis (2-DE), and the Western blotting analysis were performed probing with the Brucella-infected serm from humans, cattles and goats.The immunodominant proteins were identified by Liquid chromatography tandem mass spectrometry (LC-MS/MS).Some common immunodominant proteins recognized by the three different serum will be new immunogenic candidate proteins for the development of brucellosis subunit vaccine.
Then, these immunogenic candidate proteins were expressed in E.coli for evaluating their immunogenicity and protective ability in the mice model, which laid a foundation for obtaining really effective vaccine antigens candidates.
The corresponding results were obtained based on the above studies:
1、33 differentially expressed proteins from Brucella melitensis virulent strain 16M and vaccine strain M5 outer membrane proteins were found.The results of LC-MS/MS and bioinfermatics indicated that they represented 26 open reading frames. And 22 and 5 proteins were up-regulated in 16M and M5, respectively. The data of bioinfermation retrieval and related references showed that the up-regulated proteins in 16M mainly participated in energy metabolism, fat metabolism, protein, amino acid and polysaccharides biosynthesis and the one in M5 were important immunogenic proteins.The results of semi-quantitative RT-PCR showed that 5 Brucella memebrane proteins, which are wbkC (piont16), UTP-glucose-1-phosphate-uridylyltransferase (piont 35), purH (piont 20), Omp10 (piont 33) and sucB (piont 27), are also difference in transcription level, which basically participate in bacteria cell membrane biosynthesis.
2、The 56 immunodominant proteins were successfully identified by LC-MS/MS. Among them,11 common antigens were recognized by the serum from Brucella-infected humans, cattles and goats serum.
3、The results from the evaluation of immunogenicity and protective ablity in mice model showed that 4 of 11 immunodominant proteins, they are ahcY(piont 5), RSβ(piont 6), RSα(piont 12), Isovaleryl-CoA dehydrogenase (piont 17), could significantly induce the Th1 cell immnune response characterized by high level of IFN-γand IL-2. And they provided partially protective ability against B.melitensis 16M chanllenge, They provided the log unit protection of 2.13,1.12,1.12 and 1.24, respectively.And the protein ahcY can confer the similar profective ability(2.13) to the vaccine strain M5 (2.34).
Finally, our study provided the basis to reveal that the role of Brucella membrane protein in Brucella virulence and intracellular survival and our approaches may provide a new strategy for screening vaccine candidates in combination with immunoproteomics and analysis of the immunogenicity and protective ability in a mouse model.
引文
[1]Pappas, G., Papadimitriou, P.,2007.Challenges in Brucella bacteraemia. Int. J. Antimicrob. Agents 30(Suppl.1), S29-31.
[2]Seleem, M.N., Jain, N., Pothayee, N., Ranjan, A., Riffle, J.S., Sriranganathan, N. Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline. FEMS Microbiol Lett.2009,294,24-31.
[3]Fretin, D., Fauconnier, A., Kohler, S., Halling, S., Leonard, S., Nijskens, C., Ferooz, J., Lestrate, P., Delrue, R.M., Danese, I., Vandenhaute, J., Tibor,A., DeBolle, X., Letesson, J.J. The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection.Cell Microbiol.2005,7,687-698.
[4]Yanagi, M., Yamasato, K. Phylogenetic analysis of the family Rhizobiaceae and related bacteria by sequencing of 16S rRNA gene using PCR and DNA sequencer. FEMS Microbiol. Lett.1993,107,115-120.
[5]Bohlin J, Snipen L, Cloeckaert A, Lagesen K, Ussery D, Kristoffersen AB, Godfroid J.Genomic comparisons of Brucella spp. and closely related bacteria using base compositional and proteome based methods. BMC Evol Biol.2010,13;10:249.
[6]Jauniaux TP, Brenez C, Fretin D, Godfroid J. Haelters J, Jacques T, Kerckhof F, Mast J, Sarlet M, Coignoul FL Brucella ceti infection in harbor porpoise (Phocoena phocoena). Emerg Infect Dis.2010,16(12):1966-8.
[7]Seleem, M.N., Boyle, S.M., Sriranganathan, N. Brucella:a pathogen without classic virulence genes. Vet. Microbiol.2008,129,1-14.
[8]Verger, J.M., Grimont, F., Grimont, P.A., Grayon, M.,1987. Taxonomy of thegenus Brucella. Ann. Inst. Pasteur Microbiol.138.235-238.
[9]Sriranganathan, N., Seleem, M.N., Olsen, S.C., Samartino, L.E., Whatmore, A.M., Bricker, B., O'Callaghan, D., Halling, S.M., Crasta, O.R., Wattam,R.A., Purkayastha, A., Sobral, B.W., Snyder, E.E., Williams, K.P., Yu G-,X., Fitch, T.A., Roop, R.M., de Figueiredo, P., Boyle, S.M., He, Y., Tsolis.R.M.2009. Genome mapping and genomics in animal-associated microbes.In:Brucella, Springer (Chapter 1).
[10].DelVecchio, V.G., Kapatral, V., Redkar, R.J., Patra, G.. Mujer, C., Los, T.,Ivanova, N., Anderson. I., Bhattacharyya. A., Lykidis. A., Reznik. G.,Jablonski. L., Larsen. N., D'Souza. M., Bernal. A., Mazur. M.. Goltsman.E., Selkov. E., Elzer. P.H., Haaius, S., O'Callaghan, D., Letesson, J.J.,Haselkorn, R., Kyrpides, N., Overbeek, R. The genome sequence of the facultative intracellular pathogen Brucella melitensis. Proc. Natl.Acad. Sci. USA.2002,99,443-448.
[11]Halling, S.M., Peterson-Burch, B.D., Bricker, B.J., Zuerner, R.L., Qing, Z., Li, L.L Kapur, V., Alt, D.P., Olsen, S.C.,2005. Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis. J. Bacteriol.187,2715-2726.
[12]Paulsen, I.T., Seshadri, R., Nelson, K.E., Eisen, J.A., Heidelberg, J.F., Read,T.D., Dodson, R.J., Umayam, L., Brinkac, L.M., Beanan, M.J., Daugherty,S.C., Deboy, R.T., Durkin, A.S., Kolonay, J.F., Madupu, R., Nelson, W.C.,Ayodeji, B., Kraul, M., Shetty, J., Malek, J., Van Aken, S.E., Riedmuller, S.,Tettelin, H., Gill, S.R., White, O., Salzberg, S.L., Hoover, D.L., Lindler, L.E..Halling, S.M., Boyle, S.M., Fraser, C.M., 2002. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Proc. Natl. Acad. Sci. U.S.A.99,13148-13153.
[13]Pappas, G., Papadimitriou, P., Akritidis, N., Christou, L., Tsianos. E.V. The new global map of human brucellosis. Lancet Infect.Dis.2006b,6,91-99.
[14]Reguera, J.M., Alarcon, A., Miralles, F., Pachon, J., Juarez, C., Colmenero, J.D. Brucella endocarditis:clinical, diagnostic, and therapeutic approach. Eur. J. Clin. Microbiol. Infect. Dis.2003.22,647-650.
[15]Taleski, V., Zerva, L., Kantardjiev, T., Cvetnic, Z., Erski-Biljic, M., Nikolovski, B., Bosnjakovski. J., Katalinic-Jankovic, V., Panteliadou, A., Stojkoski, S., Kirandziski, T.An overview of the epidemiology and epizootology of brucellosis in selected countries of Central and Southeast Europe.Vet. Microbiol.2002,90,147-155.
[16]Acha, N.P., Szyfres, B.,2003.Zoonoses and Communicable Diseases Common to Man and Animals, third ed., vol. 1.Pan American Health Organization (PAHO), Washington, DC.
[17]McDonald, W.L., Jamaludin, R., Mackereth, G., Hansen, M., Humphrey, S.,Short, P., Taylor, T., Swingler, J., Dawson, C.E., Whatmore, A.M., Stubberfield, E., Perrett. L.L., Simmons, G. Characterization of a Brucella sp. strain as a marine-mammal type despite isolation from a patient with spinal osteomyelitis in New Zealand. J. Clin. Microbiol.2006,44,4363-4370
[18]Sohn. A.H., Probert. W.S., Glaser. C.A., Gupta, N., Bollen. A.W., Wong, J.D.,Grace, E.M., McDonald. W.C. Human neuro brucellosis with intracerebral granuloma caused by a marine mammal Brucella spp. Emerg. Infect. Dis.2003,9,485-488.
[19]Chain, P.S., Comerci, D.J., Tolmasky, M.E., Larimer. F.W., Malfatti,S.A.,Vergez, L.M., Aguero, F., Land, M.L., Ugalde, R.A., Garcia, E. Whole-genome analyses of speciation events in pathogenic Brucellae. Infect Immun.2005,73:8353-8361.
[20]Tabak, F., Hakko, E., Mete, B., Ozaras, R., Mert, A., Ozturk, R. Is family screening necessary in brucellosis? Infection.2008,36,575-577.
[21]De Massis, F.,Di Girolamo, A., Petrini, A., Pizzigallo, E., Giovannini, A. Correlation between animal and human brucellosis in Italy during the period 1997-2002. Clin Microbiol Infect.2005,11,632-636.
[22]Wallach, J.C., Samartino, L.E., Efron, A., Baldi, P.C. Human infection by Brucella melitensis:an outbreak attributed to contact with infected goats. FEMS Immunol. Med. Microbiol.1997,19,315-321.
[23]Dahouk, S.A., Neubauer. H., Hensel, A., Schoneberg, I., Nockler, K., Alpers.K. Merzenich, H., Stark, K., Jansen, A.Changing epidemiology of human brucellosis, Germany,1962-2005. Emerg Infect. Dis.2007,13,1895-1900.
[24]Cook, W.E., Williams, E.S., Thorne, E.T., Kreeger, T.J., Stout, G., Bardsley. K., Edwards, H., Schurig. G., Colby, L.A., Enright, F., Elzer, P.H. Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage. J. Wildl. Dis.2002,38, 18-26.
[25]Mense. M.G., Van De Verg, L.L., Bhattacharjee, A.K., Garrett. J.L., Hart, J.A. Lindler, L.E., Hadfield, T.L., Hoover. D.L.,2001.Bacteriologic and histologic features in mice after intranasal inoculation of Brucella melitensis. Am. J. Vet. Res. 62,398-405.
[26]Robichaud, S., Libman, M., Behr. M., Rubin, E. Prevention of laboratory- acquired brucellosis. Clin Infect. Dis.2004,38, e119-122.
[27]Bouza, E., Sanchez-Carrillo, C., Hernangomez, S., Gonzalez, M.J. Laboratory-acquired brucellosis:a Spanish national survey. J. Hosp.Infect.2005,61,80-83.
[28]Mantur, B.G., Amarnath, S.K., Shinde, R.S. Review of clinical and laboratory features of human brucellosis.Indian J Med Microbiol.2007,25,188-202.
[29]Khan, M.Y., Mah. M.W.. Memish, Z.A. Brucellosis in pregnant women.Clin Infect. Dis.2001,32,1172-1177.
[30]Reguera. J.M., Alarcon, A., Miralles, F., Pachon. J., Juarez, C., Colmenero, J.D. Brucella endocarditis:clinical, diagnostic, and therapeutic approach. Eur. J. Clin. Microbiol. Infect Dis.2003,22.647-650.
[31]Young, E.J.An overview of human brucellosis.Clin Infect.Dis.1995,21,283-289 (Quiz 290).
[32]Alp, E., Koc, R.K., Durak, A.C., Yildiz, O., Aygen, B., Sumerkan, B., Doganay, M. Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis [ISRCTN31053647]. BMC Infect. Dis.2006,6,72.
[33]Kato, Y., Masuda, G., Itoda, I., Imamura, A., Ajisawa, A., Negishi, M. Brucellosis in a returned traveler and his wife:probable person-toperson transmission of Brucella melitensis. J. Travel Med.2007,14,343-345.
[34]Ewalt, D.R., Payeur, J.B., Rhyan, J.C., Geer, P.L. Brucella suis biovar 1 in naturally infected cattle:a bacteriological, serological, and histological study. J. Vet Diagn. Invest.1997,9,417-420.
[35]Kahler, S.C. Brucella melitensis infection discovered in cattle for first time, goats also infected. J. Am. Vet. Med. Assoc.2000,216,648.
[36]Hamdy, M.E., Amin. A.S. Detection of Brucella species in the milk of infected cattle, sheep, goats and camels by PCR. Vet. J.2002,163,299-305.
[37]Lilenbaum. W., de Souza, G.N., Ristow, P., Moreira. M.C., Fraguas, S., Cardoso Vda, S., Oelemann. W.M.A serological study on Brucella abortus, caprine arthritis-encephalitis virus and Leptospira in dairy goats in Rio de Janeiro. Braz. Vet. J.2007,173,408-412.
[38]Glynn, M.K., Lynn, T.V. Brucellosis.J Am Vet Med. Assoc.2008,233,900-908.
[39]Musa, M.T., Eisa, M.Z., El Sanousi, E.M., Abdel Wahab, M.B., Perrett. L. Brucellosis in camels (Camelus dromedarius) in Darfur, Western Sudan. J Comp. Pathol.2008,138,151-155.
[40]Mantur, B.G., Mangalgi, S.S. Evaluation of conventional Castaneda and lysis centrifugation blood culture techniques for diagnosis of human brucellosis.J.Clin Microbiol.2004,42,4327-4328.
[41]Buchanan, T.M., Faber, L.C.2-Mercaptoethanol Brucella agglutination test: usefulness for predicting recovery from brucellosis [J].J Clin Microbiol.1980,11, 691-693.
[42]Orduna, A., Almaraz, A., Prado, A., Gutierrez, M.P., Garcia-Pascual, A., Duenas, A., Cuervo, M., Abad. R., Hernandez. B., Lorenzo, B., Bratos. M.A., Torres, A.R. Evaluation of an immunocapture-agglutination test (Brucella capt) for serodiagnosis of human brucellosis. J Clin Microbiol.2000,38,4000-4005.
[43]Kattar, M.M., Zalloua, P.A., Araj, G.F., Samaha-Kfoury, J.,Shbaklo, H., Kanj, S.S., Khalife, S., Deeb, M.Development and evaluation of realtime polymerase chain reaction assays on whole blood and paraffinembedded tissues for rapid diagnosis of human brucellosis.Diagn Microbiol Infect.Dis.2007,59,23-32.
[44]Pappas, G., Akritidis, N., Tsianos, E. Effective treatments in the management of brucellosis.Expert Opin Pharmacother.2005,6,201-209.
[45]Pappas, G., Panagopoulou, P., Christou, L., Akritidis, N. Brucella as a biological weapon. Cell Mol. Life Sci.2006a,63,2229-2236.
[46]Seleem, M.N., Jain, N., Pothayee, N., Ranjan, A., Riffle, J.S., Sriranganathan,N. Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline.FEMS Microbiol Lett.2009,294,24-31.
[47]Solera, J., Martinez-Alfaro, E., Espinosa, A.Recognition and optimum treatment of brucellosis.Drugs.1997,53,245-256.
[48]Solera.J.,Rodriguez-Zapata,M.,Geijo,P.,Largo,J.,Paulino,J.,Saez,L., Martinez-Alfaro,E. ,Sanchez,L.,Sepulveda,M. A.,Ruiz-Ribo,M.D.Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis.The GECMEI Group.Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas.Antimicrob.Agents Chemother.1995,39,2061-2067.
[49]Briones, G., Inon de Iannino, N., Roset, M., Vigliocco, A., Paulo, P.S., Ugalde, R.A. 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.
[50]Moriyon, I., Grillo, M.J., Monreal, D., Gonzalez, D., Marin, C., Lopez-Goni, I., Mainar-Jaime, R.C., Moreno, E., Blasco, J.M.Rough vaccines in animal brucellosis: structural and genetic basis and present status.Vet Res.2004,35,1-38.
[51]Adone, R., Francia, M., Ciuchini, F. Evaluation of Brucella melitensis B115 as rough-phenotype vaccine against B.melitensis and B. ovis infections. Vaccine.2008, 26,4913-4917.
[52]Monreal D, GrilloMJ, Gonzalez D, Marin CM, de Miguel MJ, et al. Characterization of Brucella abortus O-polysaccharide and core lipopolysaccharide mutants and demonstration that a complete core is required for rough vaccines to be efficient against Brucella abortus and Brucella ovis in the mouse model. Infect Immun. 2003,71:3261-3271.
[53]Godf roid F, Taminiau B, Danese I, et al.Identification of the perosamine synt hetase gene of Brucella mel itensis 16 M and involvement of lipopolysaccharide O side chain in Brucella survival in mice and in macrophages. Infect Immun,1998, 66:5485-5493.
[54]Allen CA, Adams L G, Ficht TA. Transposon derived Brucella abortus rough mutants are at tenuated and exhibit reduced intracevllular survival. Infect Immun, 1998,66:1008-1016.
[55]Vemulapalli R, McQuiston J R, Schurig GG, et al.Identification of an IS711 element interrupting the wboA gene of B rucella abortus vaccine strain RB51 and a PCR assay to distinguish strain RB51 from other Brucella species and strains.Clin Diagn Lab Immunol.1999,5:760-764.
[56]Ugalde J E, Czibener C, Feldman MF,et al.Identification and characterization of the B rucella abortus phosphoglucomutase gene:role of lipopolysaccharide in virulence and int racellular multiplication[J].Infect Immun,2000,68:5719-5723.
[57]Godf roid F, Cloeckaert A, Taminiau B, et al.Genetic organization of t he lipopolysaccharide O antigen biosynt hesis region of Brucella melitensis 16M (wbk) [J]. Res Microbiol,2000.151:655-668.
[58]Velasco J. Bengoechea J A, Brandenburg K, et al.Brucella abortus and its closest phylogenetic relative, Ochrobactrum spp, differ in outermembrane permeability and cationic pep tide resistance [J].Infect Immun,2000,68:3210-3218.
[59]Forestier C, Deleuil F, Lapaque N, et al.Brucella abortus lipopolysaccharide in murine peritonealmacrophages acts as a down regulator of T cell activation [J].J Immunol. 2000,165:5202-5210.
[60]J imenez de BaguesM P, Terraza A, Gross A, et al.Different responses ofmacrophages to smooth and rough Brucella spp.:relationship to virulence [J]. Infect Immun,2004,72:2429-2433.
[61]Manterola L, Moriyo n I, Moreno E, et al.The Lipopolysaccharide of B rucella abortus BvrS/BvrR mutants contains lipid A modifications and has higher affinity for bactericidal cationicpeptides[J]. J Bacte,2005:5631 5639.
[62]Sola-Landa A, Pizarro-Cerda J, Grillo MJ. Moreno E, Moriyon I, Blasco JM, Gorvel JP, Lopez-Goni I, 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.
[63]Lopez-Goni I, Guzman-Verri C, Manterola L, Sola-Landa A, Moriyon I, Moreno E, Regulation of Brucella virulence by the two-component system BvrR/BvrS, Vet Microbiol,2002,90:329-339.
[64]Guzman-Verri C, Manterola L, Sola-Landa A, Parra A, Cloeckaert A, Garin J, Gorvel JP, Moriyon I, Moreno E, Lopez-Goni I, 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.
[65]Taminiau B, Daykin M, Swift S, Boschiroli ML, Tibor A, Lestrate P, De Bolle X, O'Callaghan D,Williams P, Letesson JJ,.Identification of a quorum-sensing signal molecule in the facultative intracellular pathogen Brucella melitensis, Infect Immun.2002,70:3004-3011.
[66]Fuqua WC, Winans SC, Greenberg EP,. Quorum sensing in bacteria:the LuxR-LuxI family of celldensity-responsive transcriptional regulators, J Bacteriol.1994,176: 269-275.
[67]Rambow-Larsen AA, Rajashekara G, Petersen E, Splitter G.. Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the type Ⅳ secretion system and flagella, J Bacteriol,2008,190:3274-3282.
[68]Rafie-Kolpin M, Essenberg RC, Wyckoff JH,3rd, Identification and comparison of macrophage-induced proteins and proteins induced under various stress conditions in Brucella abortus. Infect Immun,1996,64:5274-5283。
[69]Teixeira-Gomes AP, Cloeckaert A, Zygmunt MS, Characterization of heat, oxidative, and acid stress responses in Brucella melitensis.Infect Immun,2000,68:2954-2961.
[70]Delory M, Hallez R, Letesson JJ, De Bolle X, An RpoH-like heat shock sigma factor is involved in stress response and virulence in Brucella melitensis 16M, J Bacteriol, 2006,188:7707-7710.
[71]Caron E, Cellier M, Liautard JP, Kohler S, Complementation of a DnaK-deficient Escherichia coli strain with the dnaK/dnaJ operon of Brucella ovis reduces the rate of initial intracellular killing within the monocytic cell line U937. FEMS Microbiol Lett.1994,120:335-340.
[72]Cellier MF, Teyssier J, Nicolas M, Liautard JP, Marti J, Sri Widada J, Cloning and characterization of the Brucella ovis heat shock protein DnaK functionally expressed in Escherichia coli.J Bacteriol.1992,174:8036-8042.
[73]Phillips RW, Roop RM,2nd:Brucella abortus HtrA functions as an authentic stress response protease but is not required for wild-type virulence in BALB/c mice. Infect Immun.2001,69:5911-5913.
[74]Elzer PH, Phillips RW, Kovach ME, Peterson KM, Roop RM,2nd, Characterization and genetic complementation of a Brucella abortus high temperature requirement A (htrA) deletion mutant.Infect Immun.1994,62:4135-4139.
[75]Phillips RW, Elzer PH, Roop RM, Ⅱ, A. Brucella melitensis high temperature requirement A (htrA) deletion mutant demonstrates a stress response defective phenotype in vitro and transient attenuation in the BALB/c mouse model.Microb Pathog.1995,19:227-284.
[76]Phillips RW. Elzer PH, Robertson GT, Hagius SD, Walker JV, Fatemi MB, Enright FM, Roop RM,2nd.A Brucella melitensis high-temperature-requirement A (htrA) deletion mutant is attenuated in goats and protects against abortion.Res Vet Sci.1997, 63:165-167.
[77]Yu DH, Hu XD, Cai H.. A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses.DNA Cell Biol.2007,26:435-443。
[78]Munoz-Montesino C, Andrews E, Rivers R, Gonzalez-Smith A, Moraga-Cid G, Folch H, Cespedes S, Onate AA, Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells.Infect Immun.2004,72:2081-2087.
[79]Porte F, Liautard J P, Kohler S. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages[J]. Infect Immun.1999,67:4041-4047.
[80]Rolan HG, den Hartigh AB, Kahl McDonagh M, et al. VirB12 is a serological marker of B rucel la infection in experimental and natural hosts[J]. Clin Vaccine Immunol.2008,15(2):208-214.
[81]Rouot B, Alvarez Martinez MT, Marius C, et al.Production oft he type IV secretion system differs among Brucella species as revealed wit h VirB5 and VirB8 Specific antisera[J]. Infect Immun.2003,71 (3):1075 1082.
[82]H ppner C. Carle A. Sivanesan D,. et al.The putative lytictransglycosylase VirBl from Brucella suis interacts wit h the type IV secretion system core components VirB8 VirB9 and VirB11[J].Microbiology.2005,151:3469-3482.
[83]Patey G, Qi Z, Bourg G, et al.Swapping of periplasmic domains between Brucella suis VirB8 and a pSB10-VirB8 homologue allows heterologous complementation[J]. Infect Immun.2006,74(8):4945-4949.
[84]Manterola L, Moriyo n I, Moreno E, et al. The Lipopolysaccharide of B rucel la abortus BvrS/BvrR mutant s contains lipid A modifications and has higher affinity for bactericidal cationicpeptides [J]. J Bacte,2005:5631-5639.
[85]Andreas B, den Hartigh, Yao2Hui Sun, et al. Differential requirements for VirB 1 and VirB2 during B rucel la abortus infection [J]. Infect Immun,2004,72(9):5143 5149.
[86]de Iannino N I, Briones G, Iannino F, et al. Osmotic regulation of cyclic 1,2-beta glucan synthesis [J]. Microbiology,2000,146:1735-1742.
[87]Briones G. Inon de Iannino N, RosetM. et al. Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular rep lication in HeLa cells [J]. Infect Immun.2001,69:4528-4535.
[88]Bohin, J P. Osmoregulated perip lasmic glucansin Proteobacteria [J].FEMS Microbiol Lett.2000,186:11-19.
[89]Edmonds M P,Cloeckaert A,Booth N J.et al.Attenuation of a Brucella abortus mutant lacking a major 25 KDa outer membrane protein in cattle[J].Am J Vet Res.2001, 62:1461-1466.
[90]Sha Z, et al.Brucella abortus is a periplasmic protein lacking a standard signal Sequence [J].J Bact.1994,176(23):73-75.
[91]Ewalt D R, Bricker B J.Validation of the abbreviated Brucella AMOS PCR as a rapid screening method for differentiation of Brucella abortus Field strain isolates and Vaccine Strains S19 and RB51[J].J Clin Microb.2000,38(8):3085-3086.
[92]Delory M, Hallez R, Letesson JJ, et al.An Rpo H-like heat shock sigma factor is involved in stress response and virulence in Brucella melitensis 16M[J].J Bacteriol.2006,188 (21):7707-10.
[93]LeVier K, Phillip s RW, Grippe V K. et al. Similar requirements of a plant symbiont and a mammalian pathogen for prolonged intracellular survival [J]. Science.2000.287: 2492-2493.
[94]Conde-Alvarez R. GrilloM J, Salcedo S P. et al. Synthesis of phosphatidylcholine, a typical eukaryotic phospholip id. is necessary for full virulence of the intracellular bacterial parasite Brucella abortus [J].CellMicrobiol.2006,8:1322-1335.
[95]Meikle P J, Perry M B, Cherwonogrodzy J W,.et al. Fine stucture of A and antigens f rom Brucel la biovars.Infect Immun.1989,57:2820-2828.
[96]Weynants V, Gilson D A, Cloeckaert A,.et al.Characteriza-tion of smooth lipopolysaccharides and O poplysaccharides of Brucella species by competition binding assays with monoclonal antibodies.Infect Immun.1997,65:1939-1943.
[97]Cloeckaert A,Weynants V,Godforid J,.etal.O-polysaccha-ride epitopic heterogeneity at the surface of Brucella spp.studied by enzyme-linked immunosorbent assay and flow cytometry.Clin Diagn Lab Immunol.1998,5(6):862-870.
[98]Garin-BastujiB, BowdenGA, dubrayG,.et al.Sodium dodecyl Sulfate polyacrylamide gel electrophoresis and immunoblotling analysis of smooth lipopolysaccharide heterogeneity among Brucella biovars related to A and M specificities.J Clin Microbiol.1990,28(10):2169-2174.
[99]Winter AJ.Outer membrane proteins of Brucella.Ann Inst Pasteur Microbiol.1987. 138(1):87-9.
[100]Sowa, B. A., K. A. Kelly, T. A. Ficht, M. Frey, and L. G. Adams.SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus.Vet Microbiol.1991,27:351-369.
[101]Tibor A, Decelle B, Letesson JJ.Outer membrane proteins Omp10, Omp16, and Omp19 of Brucella spp. are lipoproteins. Infect Immun.1999,67:4960-4962.
[102]Tibor A, Wansard V, Bielartz V, Delrue RM, Danese I, Michel P, Walravens K, Godfroid J, Letesson JJ,.Effect of omp10 or omp19 deletion on Brucella abortus outer membrane properties and virulence in mice.Infect Immun.2002.70:5540-5546.
[103]Karina A..et al.Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4+ and CD8+ T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection. Infect Immun.2009,56:436-445.
[104]Pasquevich KA, Garcia Samartino C..et al. The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Thl immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. J Immunol.2010,184(9):5200-12.
[105]Marquis, H., and T. A. Ficht.The omp2 gene locus of Brucella abortus encodes two homologous outer membrane proteins with properties characteristic of bacterial porins.Infect Immun.1993,61:3785-3790.
[106]Mobasheri, H., T. A. Ficht. H. Marquis, E. J. Lea, and J. H. Lakey.Brucella Omp2a and Omp2b porins:single channel measurements and topology prediction. FEMS Microbiol Lett.1997,155:23-30.
[107]Ficht, T. A., S. W. Bearden, B. A. Sowa, and L. G. Adams.DNA sequence and expression of the 36-kilodalton outer membrane protein gene of Brucella abortus. Infect Immun.1989,57:3281-3291.
[108]Martin-Martin AI,Caro-Hernandez P.Sancho P,Tejedor C,Cloeckaert A, Fernandez-Lago L, Vizcaino N. Analysis of the occurrence and distribution of the Omp25/Omp31 family of surface proteins in the six classical Brucella species. Vet Microbiol.2009,137 (1-2):74-82.
[109]Ficht, T. A., S. W. Bearden, B. A. Sowa, and H. Marquis.Genetic variation at the omp2 porin locus of the brucellae:species-specific markers.Mol Microbiol.1990, 4:1135-1142.
[110]Ficht, T. A., H. S. Husseinen, J. Derr, and S. W. Bearden.Species specific sequences at the omp2 locus of Brucella type strains. Int J Syst.Bacteriol.1996,46:329-331.
[111]Cloeckaert A, Vizcaino N, Paquet JY, Bowden RA, Elzer PH.Major outer membrane proteins of Brucella spp.:past, present and future.Vet Microbiol.2002,90:229-247.
[112]Jubier-Maurin V, Boigegrain RA, Cloeckaert A, Gross A, Alvarez-Martinez MT, Terraza A.Liautard J. Kohler S, Rouot B, Dornand J, Liautard JP.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.
[113]Caro-Hernandez P, Fernandez-Lago L. de Miguel MJ, Martin-Martin AI, Cloeckaert A, Grillo MJ, Vizcaino N.Role of the Omp25/Omp31 family in outer membrane properties and virulence of Brucella ovis. Infect Immun.2007,75 (8):4050-61.
[114]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.
[115]Juliana Cassataro. Silvia M. Estein, Karina A. Pasquevich,.et al.Vaccination with the Recombinant Brucella Outer Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4+ T Helper 1 Response That Protects against Brucella melitensis Infection.Infect Immun.2005,73:8079-8088.
[116]Imed Salhi.Characterization of New Members of the Group 3 Outer Membrane Protein Family of Brucella spp.Infect Immun.2003,71:4326-4332.
[117]Yu DH, Hu XD, Cai H,.A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses.DNA Cell Biol.2007,26:435-443。
[118]Pakzad I,.et al.Expression of human serum albumin--L7/L12 (Brucella abortus ribosomal protein) fusion protein in Saccharomyces cerevisiae.Pol J Microbiol.2009, 58(2):99-104.
[119]Denoel, P. A., T. K. Vo, A. Tibor, V. E. Weynants, J. M. Trunde, G. Dubray, J. N. Limet, and J. J. Letesson.Characterization, occurrence, and molecular cloning of a 39-kilodalton Brucella abortus cytoplasmic protein immunodominant in cattle.Infect Immun.1997.65:495-502.
[120]Al Mariri A,Tibor A, Mertens P,.et al.Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant.Infect Immun.2001,69 (8):4816-4822.
[121]Murphy A, Sathiyaseelan J, Parent MA..et al.Interferon gamma is crucial for surviving a Brucella abortus infection in both resistant C57BLP6 and susceptible BalbPc mice.Immunology.2001,103(4):511-518.
[122]Kamaraj G, Rajendra L, Shankar CR, Srinivasan VA.Optimization of production of Brucella abortus S19 culture in bioreactor using soyabean casein digest medium.New Microbiol.2010,33(4):319-28.
[123]Angus R.D.An evaluation of the stability of Brucella abortus strain 19 reduced dosage lyophilized vaccines produced by different methods.Dev Biol Stand.1984,56, 659-678.
[124]Mingle, C.K., Manthei, C.A., Jasmin, A.M.The stability of reduced virulence exhibited by Brucella abortus. J. Am.Vet Med Assoc.1941,99.203.
[125]Manthei. C.A.Evaluation of vaccinal methods and doses of Brucella abortus strain 19.In:Proceedings of the 56th Annual Meeting of Livestock Sanitation Association.1952, p.115.
[126]Beckett, F.W., Mc Diarmid. S.C. The effect of reduced-dose Brucella abortus strain 19 vaccination in accredited dairy herds. Br. Vet. J.1985.141.507.
[127]Elberg, S.S., Faunce, W.K. Immunization against Brucella infection. Ⅳ. Immunity conferred on goats by a non-dependant mutant from a streptomycin dependant mutant strain of Brucella melitensis. J. Bacteriol.1957,73,211.
[128]Alton, G.G.,. Rev.1 and H38 Brucella melitensis vaccines. In:Verger, J.M., Plommet, M. (Eds.), Brucella melitensis. Martinus Nijhoff, Dordrecht,1985,pp.215-227.
[129]Alton, G.G., Elberg, S.S., Crouch, D.,Rev.1 Brucella melitensis vaccine. The stability of the degree of attenuation. J. Comp. Pathol.1967,77,293-300.
[130]Fensterbank, R., Pardon, P., Marly, J.Efficacy of Brucella melitensis Rev.1 vaccine against Brucella ovis infection in rams.Ann.Rech Vet.1982,13,185-190.
[131]Van Drimmelen, C., Horwell, F.D. Preliminary findings with the use of Brucella melitensis Rev.1 as a vaccine against brucellosis in cattle. Bull. Off. Int. Epiz.1964,62, 987.
[132]Horwell, F.D., Van Drimmelen, G.G, et al. Brucella melitensis strain Rev.1 as a vaccine in cattle. S. Afr. Vet. Med. Assoc.1971,42,233-235.
[133]Garcia-Carrillo, C. Comparison of Brucella melitensis Rev.1 and B. abortus strain 19 as a vaccine against brucellosis in cattle.Zentralbl Veterinaermedicine 1980,27, 131-138.
[134]KING NB. EDGINGTON BH, FRANK NA.The use of Huddleson's Brucella M vaccine under field conditions.Am J Vet Res.1958,19(70):93-6.
[135]Xie, X.Orally administrable brucellosis vaccine:Brucella suis strain 2 vaccine.Vaccine.1986.4.212-216.
[136]Lu, S.-L., Zhang, J.-L.Brucellosis in China.In:Young, E.J., Corbel, M.J. (Eds.), Brucellosis:Clinical and Laboratory Aspects. CRC Press, Boca Raton,1989, Chapter 13, pp.173-180.
[137]Verger, J.M., Grayon, M., Zundel. E., Lechopier, P., Olivier-Bernardin, V., 1995.Comparison of the efficacy of Brucella suis strain 2 and Brucella melitensis Rev.1 live vaccines against a Brucella melitensis experimental infection in pregnant ewes.
[138]Schurig, G.G., Roop, R.M., Bagchi, T., Boyle, S., Buhrman, D., Srirangananathan, N. Biological properties of RB51; a stable rough strain of Brucella abortus. Vet Microbiol.1991,28,171-188.
[139]Surendran N. Hiltbold EM. Heid B, Sriranganathan N, Boyle SM, Zimmerman KL. Makris MR. Witonsky SG. Live Brucella abortus rough vaccine strain RB51 stimulates enhanced innate immune response in vitro compared to rough vaccine strain RB51SOD and virulent smooth strain 2308 in murine bone marrow-derived dendritic cells.Vet Microbiol.2011,47(1-2):75-82.
[140]RAMESH VEMULAPALLI, YONGQUN HE, STEPHEN M. BOYLE et al,. Brucella abortus Strain RB51 as a Vector for Heterologous Protein Expression and Induction of Specific Thl Type Immune Responses.Infect Immun.2000,68: 3290-3296.
[141]Jimenz de Bagues,Barberan M P,Marin C M,et al. The Brucella abortus RB51 vaccine does not confer protection against Brucella ovis in rams.Vaccine, 1995,13:301-304.
[142]Winter AJ. Schurig GG, Boyle SM, Sriranganathan N, Bevins JS, Enright FM, Elzer PH, Kopec JD.Protection of BALB/c mice against homologous and heterologous species of Brucella by rough strain vaccines derived from Brucella melitensis and Brucella suis biovar 4.Am J Vet Res.1996,57(5):677-83.
[143]Vemulapalli R, He Y, Buccolo LS, et a. Complementation of Brucella abortus RB51 with a functional wboA gene results in O antigen synthesis and enhanced vaccine efficacy but no change in rough phenotype and attenuation.Infect Immun.2000,68 3927-3932.
[144]Vemulapalli R, He Y, Cravero S, et al.Overexpression of protective antigen as a novel approach to enhance vaccine efficacy of Brucella abortus strain RB51. Infect Immun.2000,68:3286-3289.
[145]Kurar, E., Splitter, G.A. Nucleic acid vaccination of Brucella abortus ribosomal L7/12 gene elicits immune response.Vaccine Dec.1997,15 (17/18),1851-1857.
[146]Al-Mariri, A., Tibor, A., Mertens, P., De Bolle, X., Michel, P., Godfroid, J., Walravens, K., Letesson, J.J.Induction of immune response in BALB/c mice with a DNA vaccine encoding bacterioferritin or P39 of Brucella spp. Infect. Immun.2001, 69,6264-6270.
[147]Leclercq, S., Harms, J.S., Rosinha, G.M., Azevedo, V., Oliveira, S.C. Induction of a Thl-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene. J. Med. Microbiol.2002, 51,20-26.
[148]Velikovsky, C.A., Cassataro. J., Giambartolomei, G.H., Goldbaum, F.A., Estein, S., Bowden. R.A., Bruno. L., Fossati, C.A., Spitz. M.A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun.2002,70,2507-2511.
[149]Commander NJ, Brewer JM, Wren BW, Spencer SA, Macmillan AP, Stack JA. Liposomal delivery of p-ialB and p-omp25 DNA vaccines improves immunogenicity but fails to provide full protection against B. melitensis challenge.Genet Vaccines Ther.2010,16,8:5.
[150]Cassataro J, Velikovsky CA, de la Barrera S, Estein SM, Bruno L, Bowden R, Pasquevich KA, Fossati CA, Giambartolomei GH.A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response.Infect Immun.2005,73(10): 6537-46.
[151]Baloglu, S., T. E. Toth, G. G. Schurig, N. Sriranganathan, and S. M. Boyle. Humoral immune response of BALB/c mice to a vaccinia virus recombinant expressing Brucella abortus GroEL does not correlate with protection against a B. abortus challenge.Vet Microbiol.2000,76:193-199.
[152]Lin, J., L. G. Adams, and T. A. Ficht.Immunological response to the Brucella abortus GroEL homolog.Infect Immun.1996,64:4396-4400.
[153]Oliveira, S. C., J. S. Harms, M. Banai. and G. A. Splitter.Recombinant Brucella abortus proteins that induce proliferation and gamma-interferon secretion by CD4+T cells from Brucella-vaccinated mice and delayed-type hypersensitivity in sensitized guinea pigs.Cell. Immunol.1996,172:262-268.
[154]Oliveira, S. C., and G. A. Splitter.Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection. Vaccine.1996, 14:959-962.
[155]Roop, R. M., T. W. Fletcher, N. M. Sriranganathan, S. M. Boyle, and G. G. Schurig.Identification of an immunoreactive Brucella abortus HtrA stress response protein homolog. Infect. Immun.1994,62:1000-1007.
[156]Tabatabai, L. B., and G. W. Pugh.Modulation of immune responses in BALB/c mice vaccinated with Brucella abortus Cu-Zn superoxide dismutase synthetic peptide vaccine.Vaccine.1994,12:919-924.
[157]Kaushik P, Singh DK, Kumar SV. Tiwari AK, Shukla G, Dayal S, Chaudhuri P Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides.Vet Res Commun.2010, 34(2):119-32.
[158]Sabio y Garcia JV, Bigi F, Rossetti O, Campos E.Expression of MPB83 from Mycobacterium bovis in Brucella abortus S19 induces specific cellular immune response against the recombinant antigen in BALB/c mice.Microbes Infect.2010, 12(14-15):1236-43.
[159]Hu XD, Chen ST, Li JY, Yu DH, Yi-Zhang, Cai H. An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response.Vaccine.2010,11; 28 (12):2408-15.
[160]Jungblut P, Eckerskorn C, Lottspeich F, Klose J.Blotting efficiency investigated by using two-dimensional electrophoresis, hydrophobic membranes and proteins from different sources.Electrophoresis.1990,11(7):581-8.
[161]Klade CS.Proteomics approaches towards antigen discovery and vaccine development.Curr Opin Mol Ther.2002,4(3):216-23.
[162]Krah A, Jungblut PR.Immunoproteomics.Methods Mol Med.2004,94:19-32.
[163]Chen Z, Peng B, Wang S, Peng X.Rapid screening of highly efficient vaccine candidates by immunoproteomics.Proteomics.2004,4(10):3203-13.
[164]Jungblut PR.Proteome analysis of bacterial pathogens.Microbes Infect.2001, 3(10):831-40.
[165]Klose J.Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues.A novel approach to testing for induced point mutations in mammals.Humangenetik.1975.26(3):231-43.
[166]Klose J, von Wallenberg-Pachaly H.Changes of soluble protein populations during organogenesis of mouse embryos as revealed by protein mapping. Dev Biol.1976, 15;51(2):324-31.
[167]Herbert BR, Woods JL.Immobilised pH gradient isoelectric focusing of wool proteins.Electrophoresis.1994,15(7):972-6.
[168]Kyhse-Andersen J.Electroblotting of multiple gels:a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods.1984,10(3-4):203-9.
[169]Johansson KE.Double replica electroblotting:a method to produce two replicas from one gel.J Biochem Biophys Methods.1986,13(4-5):197-203.
[170]赵蔚,郭晓奎.病原微生物蛋白质组研究[J].微生物学免疫学进展.2004,32(1)：30.
[171]李孜,吴忠道,余新炳.病原生物基因组学和蛋白质组学在抗感染疫苗研究中的应用[J].中国热带医学.2003,3(2)：218
[172]Jungblut PR, Grabher G, Stoffler G.Comprehensive detection of immunorelevant Borrelia garinii antigens by two-dimensional electrophoresis. Electrophoresis.1999, 20(18):3611-22.
[173]Haas G, Karaali G, Ebermayer K, Metzger WG,et al.Immunoproteomics of Helicobacter pylori infection and relation to gastric disease.Proteomics.2002, 2(3):313-24.
[174]Shin GW, Palaksha KJ, Kim YR, Nho SW, Cho JH, Heo NE, Heo GJ, Park SC. Jung TS.Immunoproteomic analysis of capsulate and non-capsulate strains of Lactococcus garvieae.Vet Microbiol.2007,119(2-4):205-12.
[175]Shin GW, Palaksha KJ, Kim YR, Nho SW, Kim S, Heo GJ, Park SC, Jung TS. Application of immunoproteomics in developing a Streptococcus iniae vaccine for olive flounder (Paralichthys olivaceus).J Chromatogr B Analyt Technol Biomed Life Sci.2007.849(1-2):315-22.
[176]Shin YS, Lee EG, Shin GW, Kim YR, Lee EY, Kim JH, Jang H, Gershwin LJ, Kim DY. Kim YH, Kim GS, Suh MD, Jung TS.Identification of antigenic proteins from Neospora caninum recognized by bovine immunoglobulins M, E, A and G using immunoproteomics.Proteomics.2004,4(11):3600-9.
[177]Jagusztyn-Krynicka EK, Dadlez M. Grabowska A. Roszczenko P.Proteomic technology in the design of new effective antibacterial vaccines. Expert Rev Proteomics.2009,6(3):315-30.
[178]Chitlaru T, Gat O, Grosfeld H, Inbar I, Gozlan Y, Shafferman A.Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome.Infect Immun.2007,75(6):2841-52.
[179]Delvecchio VG, Connolly JP, Alefantis TG, Walz A, Quan MA, Patra G, Ashton JM, Whittington JT, Chafin RD. Liang X, Grewal P, Khan AS, Mujer CV.Proteomic profiling and identification of immunodominant spore antigens of Bacillus anthracis, Bacillus cereus,and Bacillus thuringiensis.Appl Environ Microbiol.2006.72(9): 6355-63.
[180]Peng X. Ye X, Wang S.Identification of novel immunogenic proteins of Shigella flexneri 2a by proteomic methodologies.Vaccine.2004,29:22(21-22):2750-6.
[181]Zhang W, Lu CP.Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2.Proteomics.2007,7(24):4468-76.
[182]党源.2型猪链球菌胞壁蛋白免疫蛋白组学研究.[硕士论文],吉林大学,2009.
[183]王斌.甲型副伤寒沙门氏菌CMCC 50973外膜蛋白的免疫蛋白质组学研究.[硕士论文],中国人民解放军军事医学科学院,2006.
[184]DelVecchio VG, Wagner MA, Eschenbrenner M, Horn TA, Kraycer JA, Estock F, Elzer P, Mujer CV.Brucella proteomes-a review. Vet Microbiol.2002,90 (1-4):593-603.
[185]Teixeira-Gomes AP, Cloeckaert A, Bezard G, Bowden RA, Dubray G, Zygmunt MS.Identification and characterization of Brucella ovis immunogenic proteins using two-dimensional electrophoresis and immunoblotting. Electrophoresis.1997, 18(8):1491-7.
[186]Connolly JP, Comerci D, Alefantis TG, Walz A, Quan M, Chafin R, Grewal P, Mujer CV, Ugalde RA, DelVecchio VG.Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development.Proteomics.2006,6(13):3767-80.
[187]Al Dahouk S, Nockler K, Scholz HC, Tomaso H, Bogumil R, Neubauer H.Immunoproteomic characterization of Brucella abortus 1119-3 preparations used for the serodiagnosis of Brucella infections.J Immunol Methods.2006,20; 309(1-2):34-47.
[188]Axel Cloeckaert.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 2004:2827-2835.
[189]Matthew Edmonds.Attenuation and immunogenicity of a Brucella abortus htrA cycL double mutant in cattle.Veterinary Microbiology,2000:81-90.
[190]DelVecchio.V.G., Kapatral,V.,Redkar,R.J.,Patra,G.et al.The genome sequence of the facultative intracellular pathogen Brucella melitensis.Proc Natl Acad Sci.2002,99, 443-448.
[191]Beatriz Arellano-Reynoso.Cyclicβ-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nature Immunology.2005:618-625.
[192]R.M.特怀曼著,王恒樑译.蛋白质组学原理[M].北京：化学工业出版社,2007.
[193]Eschenbrenner M, Wagner M A, Horn TA,et al. Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain 16M [J]. J Bacteriol.2002,184(18):4962-4970.
[194]Verstreate DR, Creasy MT, Caveney NT, Baldwin CL, Blab MW, Winter AJ. Outer membrane proteins of Brucella abortus:isolation and characterization. Infect Immun.1982,35(3):979-89.
[195]Molloy MP. Isolation of Bacterial Cell Membranes Proteins Using Carbonate Extraction.Methods in Molecular Biology 2008,424:397-402.
[196]Henningsen R GB, Straub KM, et al, Application of zwitterionic detergents to the solubilization of integral membrane proteins for two-dimensional gel electrophoresis and mass spectrometry,Proteomics,2002,2:1479-1488.
[197]Gorg A, Obermaier C, Boguth G. Harder A, Scheibe B, Wildgruber R, Weiss W, The current state of two-dimensional electrophoresis with immobilized pH gradients, Electrophoresis,2000,21:1037-1053.
[198]黄传钟.大肠杆菌膜蛋白的亚蛋白质组学分析及其膜蛋白相关复合物的研究.[硕士论文],厦门大学,2007年.
[199]Eschenbrenner M.Horn TA,Wagner MA.et al.Comparative Proteome Analysis of Laboratory Grown Brucella abortus 2308 and Brucella melitensis 16M. J Proteome Res.2006,5(7):1731-1740.
[200]赵忠鹏等.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.
[201]张洪丽.羊种布鲁氏菌强毒株16M和疫苗株M5差异蛋白质组学分析.[硕士论文].南京农业大学,2008.
[202]毛开荣,丁家波,程君生,蒋玉文,姚文生.带有氯霉素抗性基因标记的重组布氏杆菌S2的构建及其生物学特性.微生物学报,2007,47(6)：978-981.
[203]Turnquist RL, Gillett TA, Hansen RG.Uridine diphosphate glucose pyrophosphorylase.Crystallization and properties of the enzyme from rabbit liver and species comparisons.J Biol Chem.1974,249:7695-700.
[204]HARTMAN SC, BUCHANAN JM.Biosynthesis of the purines.XXVI.The identification of the formyl donors of the transformylation reactions. J Biol Chem.1959,234:1812-6.
[205]Letesson, J.-J., A. Tibor, G. van Eynde, V. Wansard, V. Weynants, P. Denoel, and E. Saman. Humoral immune responses of Brucella-infected cattle,sheep, and goats to eight purified recombinant Brucella proteins in an indirect enzyme-linked immunosorbent assay.Clin Diagn Lab.Immunol.1997,4:556-564.
[206]Tibor, A., E. Saman, P. de Wergifosse, A. Cloeckaert, J. N. Limet, and J.-J. Letesson.Molecular characterization, occurrence, and immunogenicity in infected sheep and cattle of two minor outer membrane proteins of Brucella abortus.Infect Immun.1996,64:100-107.
[207]MICHEL S. ZYGMUNT, MARI'A A. DI'AZ, et.al.Cloning, Nucleotide Sequence. and Expression of the Brucella melitensis sucB Gene Coding for an Immunogenic Dihydrolipoamide Succinyltransferase Homologous Protein. Infection and Immunity.2001, p.6537-6540.
[208]Christine M. Litwin, Joel M. Johnson, et al.The Bartonella henselae sucB gene encodes a dihydrolipoamide succinyltransferase protein reactive with sera from patients with cat-scratch disease.Journal of Medical Microbiology (2004),53, 1221-1227.
[209]Bricker B J, Ewalt D R. MacMillan A P, et al. Molecular characterization of Brucella strains isolated from marine mammals [J]. J Clin Microbial.2000,38:1258-1262.
[210]Nielsen O, Stewart R E, Nielsen K. et al. Serologic survey of Brucella spp. antibodies in some marine mammals of North America[J]. J Wildl Dis.2001,37: 89-100.
[211]Pappas G, Panagopoulou P, Christou L, et al.Brucella as a biological weapon [J]. Cell Mol Life Sci.2006,63:2229-2236.
[212]Moriyon I, GrilloM J, MonrealD, et al. Rough vaccines in animal brucellosis: structural and genetic basis and present status [J]. Vet Res,2004,35:1238.
[213]Gerhardt G.Schurig.BrucellosisVaccine:past, present, and future.Veterinary Microbiology.2002,90:479-496.
[214]Chen Z, Peng B, Wang S, Peng X.Rapid screening of highly efficient vaccine candidates by immunoproteomics.Proteomics.2004,4(10):3203-13.
[215]Vizeaino N, Cloeckaert A, Zygmunt MS, et al. Cloning, nueleotide sequence, and expression of the Brucella melitensis omp31 gene coding for an immunogenic major outer membrane protein [J].InfectImmun.1996,64(9):3744-3751.
[216]Cloeckaert A, Zygmunt MS, Bezard G, et al. Purification and antigenic analysis of the major 25-kilodalton outer membrane protein of Brucella abortus[J]. ResMierobio.1996,147(4):225-235.
[217]WinterAJ, RoweGE.Comparative immune responses to native cell envelope antigens and the hot Sodium dodecyl sulfate insoluble fraetion (PG) of Brucella abortus in cattle and mice[J].Vet Immunol Immunopathol.1988,15(2):149-163.
[218]李孜,吴忠道,余新炳.病原微生物基因组学和蛋白质组学在疫苗研究中的应用[J].中国热带医学,2003,3(2)：218.
[219]Qing-Li Wu, Yun-Feng Fu,et al. Inhibition of S-Adenosyl-L-homocysteine Hydrolase Induces Immunosuppression [J].pharmacology and experimental therapeutics.2005.313:705-711.
[220]German DC, Bloch CA, and Kredich NM.Measurements of S- adenosy -lmethionine and L-homocysteine metabolism in cultured human lymphoid cells. J Biol Chem.1983, 258:10997-11003.
[221]Wolos JA, Frondorf KA, and Esser RE.Immunosuppression mediated by an inhibitor of S-adenosyl-L-homocysteine hydrolase:prevention and treatment of collagen-induced arthritis. J Immunol.1993,151:526-534.
[222]Saso Y, Conner EM, Teegarden BR, and Yuan CS.S-Adenosyl-L-homocysteine hydrolase inhibitor mediates immunosuppressive effects in vivo:suppression of delayed type hypersensitivity ear swelling and peptidoglycan polysaccharideinduced arthritis. J Pharmacol Exp Ther.2001,296:106-112.
[223]Wolos JA, Frondorf KA, Davis GF, Jarvi ET, McCarthy JR. and Bowlin TL.Selective inhibition of T cell activation by an inhibitor of S-adenosyl-Lhomocysteine hydrolase.J Immunol.1993.150:3264-3273.
[224]Fischer M, Bacher A. et al. Biosynthesis of vitamin B2:Structure and mechanism of riboflavin synthase. Arch Biochem Biophys.2008,474:252-265.
[225]Bonomi, H. R., Marchesini, M. I., Klinke, S., Ugalde, J. E., et al., An atypical riboflavin pathway is essential for Brucella abortus virulence. PLoS One,2010,5, e9435.
[226]Goldbaum, F. A., Leoni, J., Wallach, J. C., Fossati, C. A., Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis. J Clin Microbiol 1993,31, 2141-2145.
[227]Braden, B. C., Velikovsky, C. A., Cauerhff, A. A., Polikarpov, I., Goldbaum, F. A., Divergence in macromolecular assembly:X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus. J Mol Biol.2000,297:1031-1036.
[228]Goldbaum, F. A., Velikovsky, C. A., Baldi, P. C., Mortl, S., et al. The 18-kDa cytoplasmic protein of Brucella species --an antigen useful for diagnosis--is a lumazine synthase.J Med Microbiol.1999,48,833-839.
[229]Velikovsky. C. A., Cassataro, J., Giambartolomei, G. H., Goldbaum, F. A., et al. A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice.Infect Immun.2002,70,2507-2511.
[230]Velikovsky, C. A., Goldbaum, F. A., Cassataro. J., Estein, S., et al., Brucella lumazine synthase elicits a mixed Thl-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used.Infect Immun.2003,71,5750-5755.
[231]张炜.猪链球菌2型免疫蛋白质组学和比较蛋白质组学研究.[博士论文],南京农业大学,2007.
[232]Nicoletti, P.1990. Vaccination, p.284-299. In K.Nielsen, and J. R.Duncan(ed.), Animal brucellosis.CRC Press, Boca Raton, Fla.
[233]Baldi, P. C., G. H. Giambartolomei, F. A. Goldbaum, L. F. Abdo'n. C. A. Velikovsky, R. Kittelberger, and C. A. Fossati. Humoral immune response against lipopolysaccharide and cytoplasmic proteins of Brucella abortus in cattle vaccinated with Brucella abortus S19 or experimentally infected with Yersinia enterocolitica serotype 0:9.Clin Diagn. Lab. Immunol.1996.3:472-476.
[234]Miller. M. J., R. A. Wrightsman. and J. E. Manning.Trypanosoma cruzi:protective immunity in mice immunized with paraflagellar rod proteins is associated with a T-helper type 1 response. Exp. Parasitol.1996,84:156-167.
[235]Victoratos, P., M. Yiangou, N. Avramidis, and l.Hadjipetrou.Regulation of cytokine gene expression by adjuvants in vivo.Clin Exp Immunol.1997,109:569-578.
[236]Araya, L. N., P. H. Elzer, G. H. Rowe, F. M. Enright, and A. J.Winter. Temporal development of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J. Immunol.1989,143:3330-3337.
[237]Araya, L. N., and A. J. Winter.Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum.Infect. Immun.1990,58:254-256.
[238]Cheers, C.Pathogenesis and cellular immunity in experimental murine brucellosis.Dev Biol Stand.1984,56:237-246.
[239]Eze, M. O., L. Yuan, R. M. Crawford, C. M. Paranavitana. T. L. Hadfield, A. K. Bhattacharjee, R. L. Warren, and D. L. Hoover.Effects of opsonization and gamma interferon on growth of Brucella melitensis 16M in mouse peritoneal macrophages in vitro.Infect Immun.2000.68:257-263.
[240]Murphy, E.A., J. Sathiyaseelan, M.A.Parent, B. Zou, and C.L.Baldwin. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice.Immunology.2001.103:511-518.
[241]Zhan, Y., and C. Cheers.Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect. Immun.1993,61:4899-4901.
[242]Cespedes, S., E. Andrews, H. Folch. and A. Onate.Identification and partial characterisation of a new protective antigen of Brucella abortus.J Med Microbiol. 2000,49:165-170.
[243]L.-Y.HUANG,1 A. M. KRIEG,2 N. ELLER,1 AND D. E. SCOTT1.Induction and Regulation of Thl-Inducing Cytokines by Bacterial DNA, Lipopolysacchari de, and Heat-Inactivated Bacteria.Infect. Immun,1999, p.6257-6263.
[244]MosmannTR, SadS.The expanding universe of T-cell subsets:Th1,Th2 and more.[J].Immunol Today.1996.17:138-146.
[245]Emrah Altindis, Burcu E. Tefon.et al. Immunoproteomic analysis of Bordetella pertussis and identification of new immunogenic proteins. Vaccine.2009.27: 542-548.
[246]Amy V Jennison, Rubhana Raqib, Naresh K Verma.Immunoproteome analysis of soluble and membrane proteins of Shigella fl exneri 2457T.World J Gastroenterol.2006,12(41):6683-6688.
[2]Seleem, M.N., Jain, N., Pothayee, N., Ranjan, A., Riffle, J.S., Sriranganathan, N. Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline. FEMS Microbiol Lett.2009,294,24-31.
[3]Fretin, D., Fauconnier, A., Kohler, S., Halling, S., Leonard, S., Nijskens, C., Ferooz, J., Lestrate, P., Delrue, R.M., Danese, I., Vandenhaute, J., Tibor,A., DeBolle, X., Letesson, J.J. The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection.Cell Microbiol.2005,7,687-698.
[4]Yanagi, M., Yamasato, K. Phylogenetic analysis of the family Rhizobiaceae and related bacteria by sequencing of 16S rRNA gene using PCR and DNA sequencer. FEMS Microbiol. Lett.1993,107,115-120.
[5]Bohlin J, Snipen L, Cloeckaert A, Lagesen K, Ussery D, Kristoffersen AB, Godfroid J.Genomic comparisons of Brucella spp. and closely related bacteria using base compositional and proteome based methods. BMC Evol Biol.2010,13;10:249.
[6]Jauniaux TP, Brenez C, Fretin D, Godfroid J. Haelters J, Jacques T, Kerckhof F, Mast J, Sarlet M, Coignoul FL Brucella ceti infection in harbor porpoise (Phocoena phocoena). Emerg Infect Dis.2010,16(12):1966-8.
[7]Seleem, M.N., Boyle, S.M., Sriranganathan, N. Brucella:a pathogen without classic virulence genes. Vet. Microbiol.2008,129,1-14.
[8]Verger, J.M., Grimont, F., Grimont, P.A., Grayon, M.,1987. Taxonomy of thegenus Brucella. Ann. Inst. Pasteur Microbiol.138.235-238.
[9]Sriranganathan, N., Seleem, M.N., Olsen, S.C., Samartino, L.E., Whatmore, A.M., Bricker, B., O'Callaghan, D., Halling, S.M., Crasta, O.R., Wattam,R.A., Purkayastha, A., Sobral, B.W., Snyder, E.E., Williams, K.P., Yu G-,X., Fitch, T.A., Roop, R.M., de Figueiredo, P., Boyle, S.M., He, Y., Tsolis.R.M.2009. Genome mapping and genomics in animal-associated microbes.In:Brucella, Springer (Chapter 1).
[10].DelVecchio, V.G., Kapatral, V., Redkar, R.J., Patra, G.. Mujer, C., Los, T.,Ivanova, N., Anderson. I., Bhattacharyya. A., Lykidis. A., Reznik. G.,Jablonski. L., Larsen. N., D'Souza. M., Bernal. A., Mazur. M.. Goltsman.E., Selkov. E., Elzer. P.H., Haaius, S., O'Callaghan, D., Letesson, J.J.,Haselkorn, R., Kyrpides, N., Overbeek, R. The genome sequence of the facultative intracellular pathogen Brucella melitensis. Proc. Natl.Acad. Sci. USA.2002,99,443-448.
[11]Halling, S.M., Peterson-Burch, B.D., Bricker, B.J., Zuerner, R.L., Qing, Z., Li, L.L Kapur, V., Alt, D.P., Olsen, S.C.,2005. Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis. J. Bacteriol.187,2715-2726.
[12]Paulsen, I.T., Seshadri, R., Nelson, K.E., Eisen, J.A., Heidelberg, J.F., Read,T.D., Dodson, R.J., Umayam, L., Brinkac, L.M., Beanan, M.J., Daugherty,S.C., Deboy, R.T., Durkin, A.S., Kolonay, J.F., Madupu, R., Nelson, W.C.,Ayodeji, B., Kraul, M., Shetty, J., Malek, J., Van Aken, S.E., Riedmuller, S.,Tettelin, H., Gill, S.R., White, O., Salzberg, S.L., Hoover, D.L., Lindler, L.E..Halling, S.M., Boyle, S.M., Fraser, C.M., 2002. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Proc. Natl. Acad. Sci. U.S.A.99,13148-13153.
[13]Pappas, G., Papadimitriou, P., Akritidis, N., Christou, L., Tsianos. E.V. The new global map of human brucellosis. Lancet Infect.Dis.2006b,6,91-99.
[14]Reguera, J.M., Alarcon, A., Miralles, F., Pachon, J., Juarez, C., Colmenero, J.D. Brucella endocarditis:clinical, diagnostic, and therapeutic approach. Eur. J. Clin. Microbiol. Infect. Dis.2003.22,647-650.
[15]Taleski, V., Zerva, L., Kantardjiev, T., Cvetnic, Z., Erski-Biljic, M., Nikolovski, B., Bosnjakovski. J., Katalinic-Jankovic, V., Panteliadou, A., Stojkoski, S., Kirandziski, T.An overview of the epidemiology and epizootology of brucellosis in selected countries of Central and Southeast Europe.Vet. Microbiol.2002,90,147-155.
[16]Acha, N.P., Szyfres, B.,2003.Zoonoses and Communicable Diseases Common to Man and Animals, third ed., vol. 1.Pan American Health Organization (PAHO), Washington, DC.
[17]McDonald, W.L., Jamaludin, R., Mackereth, G., Hansen, M., Humphrey, S.,Short, P., Taylor, T., Swingler, J., Dawson, C.E., Whatmore, A.M., Stubberfield, E., Perrett. L.L., Simmons, G. Characterization of a Brucella sp. strain as a marine-mammal type despite isolation from a patient with spinal osteomyelitis in New Zealand. J. Clin. Microbiol.2006,44,4363-4370
[18]Sohn. A.H., Probert. W.S., Glaser. C.A., Gupta, N., Bollen. A.W., Wong, J.D.,Grace, E.M., McDonald. W.C. Human neuro brucellosis with intracerebral granuloma caused by a marine mammal Brucella spp. Emerg. Infect. Dis.2003,9,485-488.
[19]Chain, P.S., Comerci, D.J., Tolmasky, M.E., Larimer. F.W., Malfatti,S.A.,Vergez, L.M., Aguero, F., Land, M.L., Ugalde, R.A., Garcia, E. Whole-genome analyses of speciation events in pathogenic Brucellae. Infect Immun.2005,73:8353-8361.
[20]Tabak, F., Hakko, E., Mete, B., Ozaras, R., Mert, A., Ozturk, R. Is family screening necessary in brucellosis? Infection.2008,36,575-577.
[21]De Massis, F.,Di Girolamo, A., Petrini, A., Pizzigallo, E., Giovannini, A. Correlation between animal and human brucellosis in Italy during the period 1997-2002. Clin Microbiol Infect.2005,11,632-636.
[22]Wallach, J.C., Samartino, L.E., Efron, A., Baldi, P.C. Human infection by Brucella melitensis:an outbreak attributed to contact with infected goats. FEMS Immunol. Med. Microbiol.1997,19,315-321.
[23]Dahouk, S.A., Neubauer. H., Hensel, A., Schoneberg, I., Nockler, K., Alpers.K. Merzenich, H., Stark, K., Jansen, A.Changing epidemiology of human brucellosis, Germany,1962-2005. Emerg Infect. Dis.2007,13,1895-1900.
[24]Cook, W.E., Williams, E.S., Thorne, E.T., Kreeger, T.J., Stout, G., Bardsley. K., Edwards, H., Schurig. G., Colby, L.A., Enright, F., Elzer, P.H. Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage. J. Wildl. Dis.2002,38, 18-26.
[25]Mense. M.G., Van De Verg, L.L., Bhattacharjee, A.K., Garrett. J.L., Hart, J.A. Lindler, L.E., Hadfield, T.L., Hoover. D.L.,2001.Bacteriologic and histologic features in mice after intranasal inoculation of Brucella melitensis. Am. J. Vet. Res. 62,398-405.
[26]Robichaud, S., Libman, M., Behr. M., Rubin, E. Prevention of laboratory- acquired brucellosis. Clin Infect. Dis.2004,38, e119-122.
[27]Bouza, E., Sanchez-Carrillo, C., Hernangomez, S., Gonzalez, M.J. Laboratory-acquired brucellosis:a Spanish national survey. J. Hosp.Infect.2005,61,80-83.
[28]Mantur, B.G., Amarnath, S.K., Shinde, R.S. Review of clinical and laboratory features of human brucellosis.Indian J Med Microbiol.2007,25,188-202.
[29]Khan, M.Y., Mah. M.W.. Memish, Z.A. Brucellosis in pregnant women.Clin Infect. Dis.2001,32,1172-1177.
[30]Reguera. J.M., Alarcon, A., Miralles, F., Pachon. J., Juarez, C., Colmenero, J.D. Brucella endocarditis:clinical, diagnostic, and therapeutic approach. Eur. J. Clin. Microbiol. Infect Dis.2003,22.647-650.
[31]Young, E.J.An overview of human brucellosis.Clin Infect.Dis.1995,21,283-289 (Quiz 290).
[32]Alp, E., Koc, R.K., Durak, A.C., Yildiz, O., Aygen, B., Sumerkan, B., Doganay, M. Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis [ISRCTN31053647]. BMC Infect. Dis.2006,6,72.
[33]Kato, Y., Masuda, G., Itoda, I., Imamura, A., Ajisawa, A., Negishi, M. Brucellosis in a returned traveler and his wife:probable person-toperson transmission of Brucella melitensis. J. Travel Med.2007,14,343-345.
[34]Ewalt, D.R., Payeur, J.B., Rhyan, J.C., Geer, P.L. Brucella suis biovar 1 in naturally infected cattle:a bacteriological, serological, and histological study. J. Vet Diagn. Invest.1997,9,417-420.
[35]Kahler, S.C. Brucella melitensis infection discovered in cattle for first time, goats also infected. J. Am. Vet. Med. Assoc.2000,216,648.
[36]Hamdy, M.E., Amin. A.S. Detection of Brucella species in the milk of infected cattle, sheep, goats and camels by PCR. Vet. J.2002,163,299-305.
[37]Lilenbaum. W., de Souza, G.N., Ristow, P., Moreira. M.C., Fraguas, S., Cardoso Vda, S., Oelemann. W.M.A serological study on Brucella abortus, caprine arthritis-encephalitis virus and Leptospira in dairy goats in Rio de Janeiro. Braz. Vet. J.2007,173,408-412.
[38]Glynn, M.K., Lynn, T.V. Brucellosis.J Am Vet Med. Assoc.2008,233,900-908.
[39]Musa, M.T., Eisa, M.Z., El Sanousi, E.M., Abdel Wahab, M.B., Perrett. L. Brucellosis in camels (Camelus dromedarius) in Darfur, Western Sudan. J Comp. Pathol.2008,138,151-155.
[40]Mantur, B.G., Mangalgi, S.S. Evaluation of conventional Castaneda and lysis centrifugation blood culture techniques for diagnosis of human brucellosis.J.Clin Microbiol.2004,42,4327-4328.
[41]Buchanan, T.M., Faber, L.C.2-Mercaptoethanol Brucella agglutination test: usefulness for predicting recovery from brucellosis [J].J Clin Microbiol.1980,11, 691-693.
[42]Orduna, A., Almaraz, A., Prado, A., Gutierrez, M.P., Garcia-Pascual, A., Duenas, A., Cuervo, M., Abad. R., Hernandez. B., Lorenzo, B., Bratos. M.A., Torres, A.R. Evaluation of an immunocapture-agglutination test (Brucella capt) for serodiagnosis of human brucellosis. J Clin Microbiol.2000,38,4000-4005.
[43]Kattar, M.M., Zalloua, P.A., Araj, G.F., Samaha-Kfoury, J.,Shbaklo, H., Kanj, S.S., Khalife, S., Deeb, M.Development and evaluation of realtime polymerase chain reaction assays on whole blood and paraffinembedded tissues for rapid diagnosis of human brucellosis.Diagn Microbiol Infect.Dis.2007,59,23-32.
[44]Pappas, G., Akritidis, N., Tsianos, E. Effective treatments in the management of brucellosis.Expert Opin Pharmacother.2005,6,201-209.
[45]Pappas, G., Panagopoulou, P., Christou, L., Akritidis, N. Brucella as a biological weapon. Cell Mol. Life Sci.2006a,63,2229-2236.
[46]Seleem, M.N., Jain, N., Pothayee, N., Ranjan, A., Riffle, J.S., Sriranganathan,N. Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline.FEMS Microbiol Lett.2009,294,24-31.
[47]Solera, J., Martinez-Alfaro, E., Espinosa, A.Recognition and optimum treatment of brucellosis.Drugs.1997,53,245-256.
[48]Solera.J.,Rodriguez-Zapata,M.,Geijo,P.,Largo,J.,Paulino,J.,Saez,L., Martinez-Alfaro,E. ,Sanchez,L.,Sepulveda,M. A.,Ruiz-Ribo,M.D.Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis.The GECMEI Group.Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas.Antimicrob.Agents Chemother.1995,39,2061-2067.
[49]Briones, G., Inon de Iannino, N., Roset, M., Vigliocco, A., Paulo, P.S., Ugalde, R.A. 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.
[50]Moriyon, I., Grillo, M.J., Monreal, D., Gonzalez, D., Marin, C., Lopez-Goni, I., Mainar-Jaime, R.C., Moreno, E., Blasco, J.M.Rough vaccines in animal brucellosis: structural and genetic basis and present status.Vet Res.2004,35,1-38.
[51]Adone, R., Francia, M., Ciuchini, F. Evaluation of Brucella melitensis B115 as rough-phenotype vaccine against B.melitensis and B. ovis infections. Vaccine.2008, 26,4913-4917.
[52]Monreal D, GrilloMJ, Gonzalez D, Marin CM, de Miguel MJ, et al. Characterization of Brucella abortus O-polysaccharide and core lipopolysaccharide mutants and demonstration that a complete core is required for rough vaccines to be efficient against Brucella abortus and Brucella ovis in the mouse model. Infect Immun. 2003,71:3261-3271.
[53]Godf roid F, Taminiau B, Danese I, et al.Identification of the perosamine synt hetase gene of Brucella mel itensis 16 M and involvement of lipopolysaccharide O side chain in Brucella survival in mice and in macrophages. Infect Immun,1998, 66:5485-5493.
[54]Allen CA, Adams L G, Ficht TA. Transposon derived Brucella abortus rough mutants are at tenuated and exhibit reduced intracevllular survival. Infect Immun, 1998,66:1008-1016.
[55]Vemulapalli R, McQuiston J R, Schurig GG, et al.Identification of an IS711 element interrupting the wboA gene of B rucella abortus vaccine strain RB51 and a PCR assay to distinguish strain RB51 from other Brucella species and strains.Clin Diagn Lab Immunol.1999,5:760-764.
[56]Ugalde J E, Czibener C, Feldman MF,et al.Identification and characterization of the B rucella abortus phosphoglucomutase gene:role of lipopolysaccharide in virulence and int racellular multiplication[J].Infect Immun,2000,68:5719-5723.
[57]Godf roid F, Cloeckaert A, Taminiau B, et al.Genetic organization of t he lipopolysaccharide O antigen biosynt hesis region of Brucella melitensis 16M (wbk) [J]. Res Microbiol,2000.151:655-668.
[58]Velasco J. Bengoechea J A, Brandenburg K, et al.Brucella abortus and its closest phylogenetic relative, Ochrobactrum spp, differ in outermembrane permeability and cationic pep tide resistance [J].Infect Immun,2000,68:3210-3218.
[59]Forestier C, Deleuil F, Lapaque N, et al.Brucella abortus lipopolysaccharide in murine peritonealmacrophages acts as a down regulator of T cell activation [J].J Immunol. 2000,165:5202-5210.
[60]J imenez de BaguesM P, Terraza A, Gross A, et al.Different responses ofmacrophages to smooth and rough Brucella spp.:relationship to virulence [J]. Infect Immun,2004,72:2429-2433.
[61]Manterola L, Moriyo n I, Moreno E, et al.The Lipopolysaccharide of B rucella abortus BvrS/BvrR mutants contains lipid A modifications and has higher affinity for bactericidal cationicpeptides[J]. J Bacte,2005:5631 5639.
[62]Sola-Landa A, Pizarro-Cerda J, Grillo MJ. Moreno E, Moriyon I, Blasco JM, Gorvel JP, Lopez-Goni I, 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.
[63]Lopez-Goni I, Guzman-Verri C, Manterola L, Sola-Landa A, Moriyon I, Moreno E, Regulation of Brucella virulence by the two-component system BvrR/BvrS, Vet Microbiol,2002,90:329-339.
[64]Guzman-Verri C, Manterola L, Sola-Landa A, Parra A, Cloeckaert A, Garin J, Gorvel JP, Moriyon I, Moreno E, Lopez-Goni I, 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.
[65]Taminiau B, Daykin M, Swift S, Boschiroli ML, Tibor A, Lestrate P, De Bolle X, O'Callaghan D,Williams P, Letesson JJ,.Identification of a quorum-sensing signal molecule in the facultative intracellular pathogen Brucella melitensis, Infect Immun.2002,70:3004-3011.
[66]Fuqua WC, Winans SC, Greenberg EP,. Quorum sensing in bacteria:the LuxR-LuxI family of celldensity-responsive transcriptional regulators, J Bacteriol.1994,176: 269-275.
[67]Rambow-Larsen AA, Rajashekara G, Petersen E, Splitter G.. Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the type Ⅳ secretion system and flagella, J Bacteriol,2008,190:3274-3282.
[68]Rafie-Kolpin M, Essenberg RC, Wyckoff JH,3rd, Identification and comparison of macrophage-induced proteins and proteins induced under various stress conditions in Brucella abortus. Infect Immun,1996,64:5274-5283。
[69]Teixeira-Gomes AP, Cloeckaert A, Zygmunt MS, Characterization of heat, oxidative, and acid stress responses in Brucella melitensis.Infect Immun,2000,68:2954-2961.
[70]Delory M, Hallez R, Letesson JJ, De Bolle X, An RpoH-like heat shock sigma factor is involved in stress response and virulence in Brucella melitensis 16M, J Bacteriol, 2006,188:7707-7710.
[71]Caron E, Cellier M, Liautard JP, Kohler S, Complementation of a DnaK-deficient Escherichia coli strain with the dnaK/dnaJ operon of Brucella ovis reduces the rate of initial intracellular killing within the monocytic cell line U937. FEMS Microbiol Lett.1994,120:335-340.
[72]Cellier MF, Teyssier J, Nicolas M, Liautard JP, Marti J, Sri Widada J, Cloning and characterization of the Brucella ovis heat shock protein DnaK functionally expressed in Escherichia coli.J Bacteriol.1992,174:8036-8042.
[73]Phillips RW, Roop RM,2nd:Brucella abortus HtrA functions as an authentic stress response protease but is not required for wild-type virulence in BALB/c mice. Infect Immun.2001,69:5911-5913.
[74]Elzer PH, Phillips RW, Kovach ME, Peterson KM, Roop RM,2nd, Characterization and genetic complementation of a Brucella abortus high temperature requirement A (htrA) deletion mutant.Infect Immun.1994,62:4135-4139.
[75]Phillips RW, Elzer PH, Roop RM, Ⅱ, A. Brucella melitensis high temperature requirement A (htrA) deletion mutant demonstrates a stress response defective phenotype in vitro and transient attenuation in the BALB/c mouse model.Microb Pathog.1995,19:227-284.
[76]Phillips RW. Elzer PH, Robertson GT, Hagius SD, Walker JV, Fatemi MB, Enright FM, Roop RM,2nd.A Brucella melitensis high-temperature-requirement A (htrA) deletion mutant is attenuated in goats and protects against abortion.Res Vet Sci.1997, 63:165-167.
[77]Yu DH, Hu XD, Cai H.. A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses.DNA Cell Biol.2007,26:435-443。
[78]Munoz-Montesino C, Andrews E, Rivers R, Gonzalez-Smith A, Moraga-Cid G, Folch H, Cespedes S, Onate AA, Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells.Infect Immun.2004,72:2081-2087.
[79]Porte F, Liautard J P, Kohler S. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages[J]. Infect Immun.1999,67:4041-4047.
[80]Rolan HG, den Hartigh AB, Kahl McDonagh M, et al. VirB12 is a serological marker of B rucel la infection in experimental and natural hosts[J]. Clin Vaccine Immunol.2008,15(2):208-214.
[81]Rouot B, Alvarez Martinez MT, Marius C, et al.Production oft he type IV secretion system differs among Brucella species as revealed wit h VirB5 and VirB8 Specific antisera[J]. Infect Immun.2003,71 (3):1075 1082.
[82]H ppner C. Carle A. Sivanesan D,. et al.The putative lytictransglycosylase VirBl from Brucella suis interacts wit h the type IV secretion system core components VirB8 VirB9 and VirB11[J].Microbiology.2005,151:3469-3482.
[83]Patey G, Qi Z, Bourg G, et al.Swapping of periplasmic domains between Brucella suis VirB8 and a pSB10-VirB8 homologue allows heterologous complementation[J]. Infect Immun.2006,74(8):4945-4949.
[84]Manterola L, Moriyo n I, Moreno E, et al. The Lipopolysaccharide of B rucel la abortus BvrS/BvrR mutant s contains lipid A modifications and has higher affinity for bactericidal cationicpeptides [J]. J Bacte,2005:5631-5639.
[85]Andreas B, den Hartigh, Yao2Hui Sun, et al. Differential requirements for VirB 1 and VirB2 during B rucel la abortus infection [J]. Infect Immun,2004,72(9):5143 5149.
[86]de Iannino N I, Briones G, Iannino F, et al. Osmotic regulation of cyclic 1,2-beta glucan synthesis [J]. Microbiology,2000,146:1735-1742.
[87]Briones G. Inon de Iannino N, RosetM. et al. Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular rep lication in HeLa cells [J]. Infect Immun.2001,69:4528-4535.
[88]Bohin, J P. Osmoregulated perip lasmic glucansin Proteobacteria [J].FEMS Microbiol Lett.2000,186:11-19.
[89]Edmonds M P,Cloeckaert A,Booth N J.et al.Attenuation of a Brucella abortus mutant lacking a major 25 KDa outer membrane protein in cattle[J].Am J Vet Res.2001, 62:1461-1466.
[90]Sha Z, et al.Brucella abortus is a periplasmic protein lacking a standard signal Sequence [J].J Bact.1994,176(23):73-75.
[91]Ewalt D R, Bricker B J.Validation of the abbreviated Brucella AMOS PCR as a rapid screening method for differentiation of Brucella abortus Field strain isolates and Vaccine Strains S19 and RB51[J].J Clin Microb.2000,38(8):3085-3086.
[92]Delory M, Hallez R, Letesson JJ, et al.An Rpo H-like heat shock sigma factor is involved in stress response and virulence in Brucella melitensis 16M[J].J Bacteriol.2006,188 (21):7707-10.
[93]LeVier K, Phillip s RW, Grippe V K. et al. Similar requirements of a plant symbiont and a mammalian pathogen for prolonged intracellular survival [J]. Science.2000.287: 2492-2493.
[94]Conde-Alvarez R. GrilloM J, Salcedo S P. et al. Synthesis of phosphatidylcholine, a typical eukaryotic phospholip id. is necessary for full virulence of the intracellular bacterial parasite Brucella abortus [J].CellMicrobiol.2006,8:1322-1335.
[95]Meikle P J, Perry M B, Cherwonogrodzy J W,.et al. Fine stucture of A and antigens f rom Brucel la biovars.Infect Immun.1989,57:2820-2828.
[96]Weynants V, Gilson D A, Cloeckaert A,.et al.Characteriza-tion of smooth lipopolysaccharides and O poplysaccharides of Brucella species by competition binding assays with monoclonal antibodies.Infect Immun.1997,65:1939-1943.
[97]Cloeckaert A,Weynants V,Godforid J,.etal.O-polysaccha-ride epitopic heterogeneity at the surface of Brucella spp.studied by enzyme-linked immunosorbent assay and flow cytometry.Clin Diagn Lab Immunol.1998,5(6):862-870.
[98]Garin-BastujiB, BowdenGA, dubrayG,.et al.Sodium dodecyl Sulfate polyacrylamide gel electrophoresis and immunoblotling analysis of smooth lipopolysaccharide heterogeneity among Brucella biovars related to A and M specificities.J Clin Microbiol.1990,28(10):2169-2174.
[99]Winter AJ.Outer membrane proteins of Brucella.Ann Inst Pasteur Microbiol.1987. 138(1):87-9.
[100]Sowa, B. A., K. A. Kelly, T. A. Ficht, M. Frey, and L. G. Adams.SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus.Vet Microbiol.1991,27:351-369.
[101]Tibor A, Decelle B, Letesson JJ.Outer membrane proteins Omp10, Omp16, and Omp19 of Brucella spp. are lipoproteins. Infect Immun.1999,67:4960-4962.
[102]Tibor A, Wansard V, Bielartz V, Delrue RM, Danese I, Michel P, Walravens K, Godfroid J, Letesson JJ,.Effect of omp10 or omp19 deletion on Brucella abortus outer membrane properties and virulence in mice.Infect Immun.2002.70:5540-5546.
[103]Karina A..et al.Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4+ and CD8+ T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection. Infect Immun.2009,56:436-445.
[104]Pasquevich KA, Garcia Samartino C..et al. The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Thl immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. J Immunol.2010,184(9):5200-12.
[105]Marquis, H., and T. A. Ficht.The omp2 gene locus of Brucella abortus encodes two homologous outer membrane proteins with properties characteristic of bacterial porins.Infect Immun.1993,61:3785-3790.
[106]Mobasheri, H., T. A. Ficht. H. Marquis, E. J. Lea, and J. H. Lakey.Brucella Omp2a and Omp2b porins:single channel measurements and topology prediction. FEMS Microbiol Lett.1997,155:23-30.
[107]Ficht, T. A., S. W. Bearden, B. A. Sowa, and L. G. Adams.DNA sequence and expression of the 36-kilodalton outer membrane protein gene of Brucella abortus. Infect Immun.1989,57:3281-3291.
[108]Martin-Martin AI,Caro-Hernandez P.Sancho P,Tejedor C,Cloeckaert A, Fernandez-Lago L, Vizcaino N. Analysis of the occurrence and distribution of the Omp25/Omp31 family of surface proteins in the six classical Brucella species. Vet Microbiol.2009,137 (1-2):74-82.
[109]Ficht, T. A., S. W. Bearden, B. A. Sowa, and H. Marquis.Genetic variation at the omp2 porin locus of the brucellae:species-specific markers.Mol Microbiol.1990, 4:1135-1142.
[110]Ficht, T. A., H. S. Husseinen, J. Derr, and S. W. Bearden.Species specific sequences at the omp2 locus of Brucella type strains. Int J Syst.Bacteriol.1996,46:329-331.
[111]Cloeckaert A, Vizcaino N, Paquet JY, Bowden RA, Elzer PH.Major outer membrane proteins of Brucella spp.:past, present and future.Vet Microbiol.2002,90:229-247.
[112]Jubier-Maurin V, Boigegrain RA, Cloeckaert A, Gross A, Alvarez-Martinez MT, Terraza A.Liautard J. Kohler S, Rouot B, Dornand J, Liautard JP.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.
[113]Caro-Hernandez P, Fernandez-Lago L. de Miguel MJ, Martin-Martin AI, Cloeckaert A, Grillo MJ, Vizcaino N.Role of the Omp25/Omp31 family in outer membrane properties and virulence of Brucella ovis. Infect Immun.2007,75 (8):4050-61.
[114]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.
[115]Juliana Cassataro. Silvia M. Estein, Karina A. Pasquevich,.et al.Vaccination with the Recombinant Brucella Outer Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4+ T Helper 1 Response That Protects against Brucella melitensis Infection.Infect Immun.2005,73:8079-8088.
[116]Imed Salhi.Characterization of New Members of the Group 3 Outer Membrane Protein Family of Brucella spp.Infect Immun.2003,71:4326-4332.
[117]Yu DH, Hu XD, Cai H,.A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses.DNA Cell Biol.2007,26:435-443。
[118]Pakzad I,.et al.Expression of human serum albumin--L7/L12 (Brucella abortus ribosomal protein) fusion protein in Saccharomyces cerevisiae.Pol J Microbiol.2009, 58(2):99-104.
[119]Denoel, P. A., T. K. Vo, A. Tibor, V. E. Weynants, J. M. Trunde, G. Dubray, J. N. Limet, and J. J. Letesson.Characterization, occurrence, and molecular cloning of a 39-kilodalton Brucella abortus cytoplasmic protein immunodominant in cattle.Infect Immun.1997.65:495-502.
[120]Al Mariri A,Tibor A, Mertens P,.et al.Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant.Infect Immun.2001,69 (8):4816-4822.
[121]Murphy A, Sathiyaseelan J, Parent MA..et al.Interferon gamma is crucial for surviving a Brucella abortus infection in both resistant C57BLP6 and susceptible BalbPc mice.Immunology.2001,103(4):511-518.
[122]Kamaraj G, Rajendra L, Shankar CR, Srinivasan VA.Optimization of production of Brucella abortus S19 culture in bioreactor using soyabean casein digest medium.New Microbiol.2010,33(4):319-28.
[123]Angus R.D.An evaluation of the stability of Brucella abortus strain 19 reduced dosage lyophilized vaccines produced by different methods.Dev Biol Stand.1984,56, 659-678.
[124]Mingle, C.K., Manthei, C.A., Jasmin, A.M.The stability of reduced virulence exhibited by Brucella abortus. J. Am.Vet Med Assoc.1941,99.203.
[125]Manthei. C.A.Evaluation of vaccinal methods and doses of Brucella abortus strain 19.In:Proceedings of the 56th Annual Meeting of Livestock Sanitation Association.1952, p.115.
[126]Beckett, F.W., Mc Diarmid. S.C. The effect of reduced-dose Brucella abortus strain 19 vaccination in accredited dairy herds. Br. Vet. J.1985.141.507.
[127]Elberg, S.S., Faunce, W.K. Immunization against Brucella infection. Ⅳ. Immunity conferred on goats by a non-dependant mutant from a streptomycin dependant mutant strain of Brucella melitensis. J. Bacteriol.1957,73,211.
[128]Alton, G.G.,. Rev.1 and H38 Brucella melitensis vaccines. In:Verger, J.M., Plommet, M. (Eds.), Brucella melitensis. Martinus Nijhoff, Dordrecht,1985,pp.215-227.
[129]Alton, G.G., Elberg, S.S., Crouch, D.,Rev.1 Brucella melitensis vaccine. The stability of the degree of attenuation. J. Comp. Pathol.1967,77,293-300.
[130]Fensterbank, R., Pardon, P., Marly, J.Efficacy of Brucella melitensis Rev.1 vaccine against Brucella ovis infection in rams.Ann.Rech Vet.1982,13,185-190.
[131]Van Drimmelen, C., Horwell, F.D. Preliminary findings with the use of Brucella melitensis Rev.1 as a vaccine against brucellosis in cattle. Bull. Off. Int. Epiz.1964,62, 987.
[132]Horwell, F.D., Van Drimmelen, G.G, et al. Brucella melitensis strain Rev.1 as a vaccine in cattle. S. Afr. Vet. Med. Assoc.1971,42,233-235.
[133]Garcia-Carrillo, C. Comparison of Brucella melitensis Rev.1 and B. abortus strain 19 as a vaccine against brucellosis in cattle.Zentralbl Veterinaermedicine 1980,27, 131-138.
[134]KING NB. EDGINGTON BH, FRANK NA.The use of Huddleson's Brucella M vaccine under field conditions.Am J Vet Res.1958,19(70):93-6.
[135]Xie, X.Orally administrable brucellosis vaccine:Brucella suis strain 2 vaccine.Vaccine.1986.4.212-216.
[136]Lu, S.-L., Zhang, J.-L.Brucellosis in China.In:Young, E.J., Corbel, M.J. (Eds.), Brucellosis:Clinical and Laboratory Aspects. CRC Press, Boca Raton,1989, Chapter 13, pp.173-180.
[137]Verger, J.M., Grayon, M., Zundel. E., Lechopier, P., Olivier-Bernardin, V., 1995.Comparison of the efficacy of Brucella suis strain 2 and Brucella melitensis Rev.1 live vaccines against a Brucella melitensis experimental infection in pregnant ewes.
[138]Schurig, G.G., Roop, R.M., Bagchi, T., Boyle, S., Buhrman, D., Srirangananathan, N. Biological properties of RB51; a stable rough strain of Brucella abortus. Vet Microbiol.1991,28,171-188.
[139]Surendran N. Hiltbold EM. Heid B, Sriranganathan N, Boyle SM, Zimmerman KL. Makris MR. Witonsky SG. Live Brucella abortus rough vaccine strain RB51 stimulates enhanced innate immune response in vitro compared to rough vaccine strain RB51SOD and virulent smooth strain 2308 in murine bone marrow-derived dendritic cells.Vet Microbiol.2011,47(1-2):75-82.
[140]RAMESH VEMULAPALLI, YONGQUN HE, STEPHEN M. BOYLE et al,. Brucella abortus Strain RB51 as a Vector for Heterologous Protein Expression and Induction of Specific Thl Type Immune Responses.Infect Immun.2000,68: 3290-3296.
[141]Jimenz de Bagues,Barberan M P,Marin C M,et al. The Brucella abortus RB51 vaccine does not confer protection against Brucella ovis in rams.Vaccine, 1995,13:301-304.
[142]Winter AJ. Schurig GG, Boyle SM, Sriranganathan N, Bevins JS, Enright FM, Elzer PH, Kopec JD.Protection of BALB/c mice against homologous and heterologous species of Brucella by rough strain vaccines derived from Brucella melitensis and Brucella suis biovar 4.Am J Vet Res.1996,57(5):677-83.
[143]Vemulapalli R, He Y, Buccolo LS, et a. Complementation of Brucella abortus RB51 with a functional wboA gene results in O antigen synthesis and enhanced vaccine efficacy but no change in rough phenotype and attenuation.Infect Immun.2000,68 3927-3932.
[144]Vemulapalli R, He Y, Cravero S, et al.Overexpression of protective antigen as a novel approach to enhance vaccine efficacy of Brucella abortus strain RB51. Infect Immun.2000,68:3286-3289.
[145]Kurar, E., Splitter, G.A. Nucleic acid vaccination of Brucella abortus ribosomal L7/12 gene elicits immune response.Vaccine Dec.1997,15 (17/18),1851-1857.
[146]Al-Mariri, A., Tibor, A., Mertens, P., De Bolle, X., Michel, P., Godfroid, J., Walravens, K., Letesson, J.J.Induction of immune response in BALB/c mice with a DNA vaccine encoding bacterioferritin or P39 of Brucella spp. Infect. Immun.2001, 69,6264-6270.
[147]Leclercq, S., Harms, J.S., Rosinha, G.M., Azevedo, V., Oliveira, S.C. Induction of a Thl-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene. J. Med. Microbiol.2002, 51,20-26.
[148]Velikovsky, C.A., Cassataro. J., Giambartolomei, G.H., Goldbaum, F.A., Estein, S., Bowden. R.A., Bruno. L., Fossati, C.A., Spitz. M.A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun.2002,70,2507-2511.
[149]Commander NJ, Brewer JM, Wren BW, Spencer SA, Macmillan AP, Stack JA. Liposomal delivery of p-ialB and p-omp25 DNA vaccines improves immunogenicity but fails to provide full protection against B. melitensis challenge.Genet Vaccines Ther.2010,16,8:5.
[150]Cassataro J, Velikovsky CA, de la Barrera S, Estein SM, Bruno L, Bowden R, Pasquevich KA, Fossati CA, Giambartolomei GH.A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response.Infect Immun.2005,73(10): 6537-46.
[151]Baloglu, S., T. E. Toth, G. G. Schurig, N. Sriranganathan, and S. M. Boyle. Humoral immune response of BALB/c mice to a vaccinia virus recombinant expressing Brucella abortus GroEL does not correlate with protection against a B. abortus challenge.Vet Microbiol.2000,76:193-199.
[152]Lin, J., L. G. Adams, and T. A. Ficht.Immunological response to the Brucella abortus GroEL homolog.Infect Immun.1996,64:4396-4400.
[153]Oliveira, S. C., J. S. Harms, M. Banai. and G. A. Splitter.Recombinant Brucella abortus proteins that induce proliferation and gamma-interferon secretion by CD4+T cells from Brucella-vaccinated mice and delayed-type hypersensitivity in sensitized guinea pigs.Cell. Immunol.1996,172:262-268.
[154]Oliveira, S. C., and G. A. Splitter.Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection. Vaccine.1996, 14:959-962.
[155]Roop, R. M., T. W. Fletcher, N. M. Sriranganathan, S. M. Boyle, and G. G. Schurig.Identification of an immunoreactive Brucella abortus HtrA stress response protein homolog. Infect. Immun.1994,62:1000-1007.
[156]Tabatabai, L. B., and G. W. Pugh.Modulation of immune responses in BALB/c mice vaccinated with Brucella abortus Cu-Zn superoxide dismutase synthetic peptide vaccine.Vaccine.1994,12:919-924.
[157]Kaushik P, Singh DK, Kumar SV. Tiwari AK, Shukla G, Dayal S, Chaudhuri P Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides.Vet Res Commun.2010, 34(2):119-32.
[158]Sabio y Garcia JV, Bigi F, Rossetti O, Campos E.Expression of MPB83 from Mycobacterium bovis in Brucella abortus S19 induces specific cellular immune response against the recombinant antigen in BALB/c mice.Microbes Infect.2010, 12(14-15):1236-43.
[159]Hu XD, Chen ST, Li JY, Yu DH, Yi-Zhang, Cai H. An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response.Vaccine.2010,11; 28 (12):2408-15.
[160]Jungblut P, Eckerskorn C, Lottspeich F, Klose J.Blotting efficiency investigated by using two-dimensional electrophoresis, hydrophobic membranes and proteins from different sources.Electrophoresis.1990,11(7):581-8.
[161]Klade CS.Proteomics approaches towards antigen discovery and vaccine development.Curr Opin Mol Ther.2002,4(3):216-23.
[162]Krah A, Jungblut PR.Immunoproteomics.Methods Mol Med.2004,94:19-32.
[163]Chen Z, Peng B, Wang S, Peng X.Rapid screening of highly efficient vaccine candidates by immunoproteomics.Proteomics.2004,4(10):3203-13.
[164]Jungblut PR.Proteome analysis of bacterial pathogens.Microbes Infect.2001, 3(10):831-40.
[165]Klose J.Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues.A novel approach to testing for induced point mutations in mammals.Humangenetik.1975.26(3):231-43.
[166]Klose J, von Wallenberg-Pachaly H.Changes of soluble protein populations during organogenesis of mouse embryos as revealed by protein mapping. Dev Biol.1976, 15;51(2):324-31.
[167]Herbert BR, Woods JL.Immobilised pH gradient isoelectric focusing of wool proteins.Electrophoresis.1994,15(7):972-6.
[168]Kyhse-Andersen J.Electroblotting of multiple gels:a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods.1984,10(3-4):203-9.
[169]Johansson KE.Double replica electroblotting:a method to produce two replicas from one gel.J Biochem Biophys Methods.1986,13(4-5):197-203.
[170]赵蔚,郭晓奎.病原微生物蛋白质组研究[J].微生物学免疫学进展.2004,32(1)：30.
[171]李孜,吴忠道,余新炳.病原生物基因组学和蛋白质组学在抗感染疫苗研究中的应用[J].中国热带医学.2003,3(2)：218
[172]Jungblut PR, Grabher G, Stoffler G.Comprehensive detection of immunorelevant Borrelia garinii antigens by two-dimensional electrophoresis. Electrophoresis.1999, 20(18):3611-22.
[173]Haas G, Karaali G, Ebermayer K, Metzger WG,et al.Immunoproteomics of Helicobacter pylori infection and relation to gastric disease.Proteomics.2002, 2(3):313-24.
[174]Shin GW, Palaksha KJ, Kim YR, Nho SW, Cho JH, Heo NE, Heo GJ, Park SC. Jung TS.Immunoproteomic analysis of capsulate and non-capsulate strains of Lactococcus garvieae.Vet Microbiol.2007,119(2-4):205-12.
[175]Shin GW, Palaksha KJ, Kim YR, Nho SW, Kim S, Heo GJ, Park SC, Jung TS. Application of immunoproteomics in developing a Streptococcus iniae vaccine for olive flounder (Paralichthys olivaceus).J Chromatogr B Analyt Technol Biomed Life Sci.2007.849(1-2):315-22.
[176]Shin YS, Lee EG, Shin GW, Kim YR, Lee EY, Kim JH, Jang H, Gershwin LJ, Kim DY. Kim YH, Kim GS, Suh MD, Jung TS.Identification of antigenic proteins from Neospora caninum recognized by bovine immunoglobulins M, E, A and G using immunoproteomics.Proteomics.2004,4(11):3600-9.
[177]Jagusztyn-Krynicka EK, Dadlez M. Grabowska A. Roszczenko P.Proteomic technology in the design of new effective antibacterial vaccines. Expert Rev Proteomics.2009,6(3):315-30.
[178]Chitlaru T, Gat O, Grosfeld H, Inbar I, Gozlan Y, Shafferman A.Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome.Infect Immun.2007,75(6):2841-52.
[179]Delvecchio VG, Connolly JP, Alefantis TG, Walz A, Quan MA, Patra G, Ashton JM, Whittington JT, Chafin RD. Liang X, Grewal P, Khan AS, Mujer CV.Proteomic profiling and identification of immunodominant spore antigens of Bacillus anthracis, Bacillus cereus,and Bacillus thuringiensis.Appl Environ Microbiol.2006.72(9): 6355-63.
[180]Peng X. Ye X, Wang S.Identification of novel immunogenic proteins of Shigella flexneri 2a by proteomic methodologies.Vaccine.2004,29:22(21-22):2750-6.
[181]Zhang W, Lu CP.Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2.Proteomics.2007,7(24):4468-76.
[182]党源.2型猪链球菌胞壁蛋白免疫蛋白组学研究.[硕士论文],吉林大学,2009.
[183]王斌.甲型副伤寒沙门氏菌CMCC 50973外膜蛋白的免疫蛋白质组学研究.[硕士论文],中国人民解放军军事医学科学院,2006.
[184]DelVecchio VG, Wagner MA, Eschenbrenner M, Horn TA, Kraycer JA, Estock F, Elzer P, Mujer CV.Brucella proteomes-a review. Vet Microbiol.2002,90 (1-4):593-603.
[185]Teixeira-Gomes AP, Cloeckaert A, Bezard G, Bowden RA, Dubray G, Zygmunt MS.Identification and characterization of Brucella ovis immunogenic proteins using two-dimensional electrophoresis and immunoblotting. Electrophoresis.1997, 18(8):1491-7.
[186]Connolly JP, Comerci D, Alefantis TG, Walz A, Quan M, Chafin R, Grewal P, Mujer CV, Ugalde RA, DelVecchio VG.Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development.Proteomics.2006,6(13):3767-80.
[187]Al Dahouk S, Nockler K, Scholz HC, Tomaso H, Bogumil R, Neubauer H.Immunoproteomic characterization of Brucella abortus 1119-3 preparations used for the serodiagnosis of Brucella infections.J Immunol Methods.2006,20; 309(1-2):34-47.
[188]Axel Cloeckaert.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 2004:2827-2835.
[189]Matthew Edmonds.Attenuation and immunogenicity of a Brucella abortus htrA cycL double mutant in cattle.Veterinary Microbiology,2000:81-90.
[190]DelVecchio.V.G., Kapatral,V.,Redkar,R.J.,Patra,G.et al.The genome sequence of the facultative intracellular pathogen Brucella melitensis.Proc Natl Acad Sci.2002,99, 443-448.
[191]Beatriz Arellano-Reynoso.Cyclicβ-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nature Immunology.2005:618-625.
[192]R.M.特怀曼著,王恒樑译.蛋白质组学原理[M].北京：化学工业出版社,2007.
[193]Eschenbrenner M, Wagner M A, Horn TA,et al. Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain 16M [J]. J Bacteriol.2002,184(18):4962-4970.
[194]Verstreate DR, Creasy MT, Caveney NT, Baldwin CL, Blab MW, Winter AJ. Outer membrane proteins of Brucella abortus:isolation and characterization. Infect Immun.1982,35(3):979-89.
[195]Molloy MP. Isolation of Bacterial Cell Membranes Proteins Using Carbonate Extraction.Methods in Molecular Biology 2008,424:397-402.
[196]Henningsen R GB, Straub KM, et al, Application of zwitterionic detergents to the solubilization of integral membrane proteins for two-dimensional gel electrophoresis and mass spectrometry,Proteomics,2002,2:1479-1488.
[197]Gorg A, Obermaier C, Boguth G. Harder A, Scheibe B, Wildgruber R, Weiss W, The current state of two-dimensional electrophoresis with immobilized pH gradients, Electrophoresis,2000,21:1037-1053.
[198]黄传钟.大肠杆菌膜蛋白的亚蛋白质组学分析及其膜蛋白相关复合物的研究.[硕士论文],厦门大学,2007年.
[199]Eschenbrenner M.Horn TA,Wagner MA.et al.Comparative Proteome Analysis of Laboratory Grown Brucella abortus 2308 and Brucella melitensis 16M. J Proteome Res.2006,5(7):1731-1740.
[200]赵忠鹏等.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.
[201]张洪丽.羊种布鲁氏菌强毒株16M和疫苗株M5差异蛋白质组学分析.[硕士论文].南京农业大学,2008.
[202]毛开荣,丁家波,程君生,蒋玉文,姚文生.带有氯霉素抗性基因标记的重组布氏杆菌S2的构建及其生物学特性.微生物学报,2007,47(6)：978-981.
[203]Turnquist RL, Gillett TA, Hansen RG.Uridine diphosphate glucose pyrophosphorylase.Crystallization and properties of the enzyme from rabbit liver and species comparisons.J Biol Chem.1974,249:7695-700.
[204]HARTMAN SC, BUCHANAN JM.Biosynthesis of the purines.XXVI.The identification of the formyl donors of the transformylation reactions. J Biol Chem.1959,234:1812-6.
[205]Letesson, J.-J., A. Tibor, G. van Eynde, V. Wansard, V. Weynants, P. Denoel, and E. Saman. Humoral immune responses of Brucella-infected cattle,sheep, and goats to eight purified recombinant Brucella proteins in an indirect enzyme-linked immunosorbent assay.Clin Diagn Lab.Immunol.1997,4:556-564.
[206]Tibor, A., E. Saman, P. de Wergifosse, A. Cloeckaert, J. N. Limet, and J.-J. Letesson.Molecular characterization, occurrence, and immunogenicity in infected sheep and cattle of two minor outer membrane proteins of Brucella abortus.Infect Immun.1996,64:100-107.
[207]MICHEL S. ZYGMUNT, MARI'A A. DI'AZ, et.al.Cloning, Nucleotide Sequence. and Expression of the Brucella melitensis sucB Gene Coding for an Immunogenic Dihydrolipoamide Succinyltransferase Homologous Protein. Infection and Immunity.2001, p.6537-6540.
[208]Christine M. Litwin, Joel M. Johnson, et al.The Bartonella henselae sucB gene encodes a dihydrolipoamide succinyltransferase protein reactive with sera from patients with cat-scratch disease.Journal of Medical Microbiology (2004),53, 1221-1227.
[209]Bricker B J, Ewalt D R. MacMillan A P, et al. Molecular characterization of Brucella strains isolated from marine mammals [J]. J Clin Microbial.2000,38:1258-1262.
[210]Nielsen O, Stewart R E, Nielsen K. et al. Serologic survey of Brucella spp. antibodies in some marine mammals of North America[J]. J Wildl Dis.2001,37: 89-100.
[211]Pappas G, Panagopoulou P, Christou L, et al.Brucella as a biological weapon [J]. Cell Mol Life Sci.2006,63:2229-2236.
[212]Moriyon I, GrilloM J, MonrealD, et al. Rough vaccines in animal brucellosis: structural and genetic basis and present status [J]. Vet Res,2004,35:1238.
[213]Gerhardt G.Schurig.BrucellosisVaccine:past, present, and future.Veterinary Microbiology.2002,90:479-496.
[214]Chen Z, Peng B, Wang S, Peng X.Rapid screening of highly efficient vaccine candidates by immunoproteomics.Proteomics.2004,4(10):3203-13.
[215]Vizeaino N, Cloeckaert A, Zygmunt MS, et al. Cloning, nueleotide sequence, and expression of the Brucella melitensis omp31 gene coding for an immunogenic major outer membrane protein [J].InfectImmun.1996,64(9):3744-3751.
[216]Cloeckaert A, Zygmunt MS, Bezard G, et al. Purification and antigenic analysis of the major 25-kilodalton outer membrane protein of Brucella abortus[J]. ResMierobio.1996,147(4):225-235.
[217]WinterAJ, RoweGE.Comparative immune responses to native cell envelope antigens and the hot Sodium dodecyl sulfate insoluble fraetion (PG) of Brucella abortus in cattle and mice[J].Vet Immunol Immunopathol.1988,15(2):149-163.
[218]李孜,吴忠道,余新炳.病原微生物基因组学和蛋白质组学在疫苗研究中的应用[J].中国热带医学,2003,3(2)：218.
[219]Qing-Li Wu, Yun-Feng Fu,et al. Inhibition of S-Adenosyl-L-homocysteine Hydrolase Induces Immunosuppression [J].pharmacology and experimental therapeutics.2005.313:705-711.
[220]German DC, Bloch CA, and Kredich NM.Measurements of S- adenosy -lmethionine and L-homocysteine metabolism in cultured human lymphoid cells. J Biol Chem.1983, 258:10997-11003.
[221]Wolos JA, Frondorf KA, and Esser RE.Immunosuppression mediated by an inhibitor of S-adenosyl-L-homocysteine hydrolase:prevention and treatment of collagen-induced arthritis. J Immunol.1993,151:526-534.
[222]Saso Y, Conner EM, Teegarden BR, and Yuan CS.S-Adenosyl-L-homocysteine hydrolase inhibitor mediates immunosuppressive effects in vivo:suppression of delayed type hypersensitivity ear swelling and peptidoglycan polysaccharideinduced arthritis. J Pharmacol Exp Ther.2001,296:106-112.
[223]Wolos JA, Frondorf KA, Davis GF, Jarvi ET, McCarthy JR. and Bowlin TL.Selective inhibition of T cell activation by an inhibitor of S-adenosyl-Lhomocysteine hydrolase.J Immunol.1993.150:3264-3273.
[224]Fischer M, Bacher A. et al. Biosynthesis of vitamin B2:Structure and mechanism of riboflavin synthase. Arch Biochem Biophys.2008,474:252-265.
[225]Bonomi, H. R., Marchesini, M. I., Klinke, S., Ugalde, J. E., et al., An atypical riboflavin pathway is essential for Brucella abortus virulence. PLoS One,2010,5, e9435.
[226]Goldbaum, F. A., Leoni, J., Wallach, J. C., Fossati, C. A., Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis. J Clin Microbiol 1993,31, 2141-2145.
[227]Braden, B. C., Velikovsky, C. A., Cauerhff, A. A., Polikarpov, I., Goldbaum, F. A., Divergence in macromolecular assembly:X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus. J Mol Biol.2000,297:1031-1036.
[228]Goldbaum, F. A., Velikovsky, C. A., Baldi, P. C., Mortl, S., et al. The 18-kDa cytoplasmic protein of Brucella species --an antigen useful for diagnosis--is a lumazine synthase.J Med Microbiol.1999,48,833-839.
[229]Velikovsky. C. A., Cassataro, J., Giambartolomei, G. H., Goldbaum, F. A., et al. A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice.Infect Immun.2002,70,2507-2511.
[230]Velikovsky, C. A., Goldbaum, F. A., Cassataro. J., Estein, S., et al., Brucella lumazine synthase elicits a mixed Thl-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used.Infect Immun.2003,71,5750-5755.
[231]张炜.猪链球菌2型免疫蛋白质组学和比较蛋白质组学研究.[博士论文],南京农业大学,2007.
[232]Nicoletti, P.1990. Vaccination, p.284-299. In K.Nielsen, and J. R.Duncan(ed.), Animal brucellosis.CRC Press, Boca Raton, Fla.
[233]Baldi, P. C., G. H. Giambartolomei, F. A. Goldbaum, L. F. Abdo'n. C. A. Velikovsky, R. Kittelberger, and C. A. Fossati. Humoral immune response against lipopolysaccharide and cytoplasmic proteins of Brucella abortus in cattle vaccinated with Brucella abortus S19 or experimentally infected with Yersinia enterocolitica serotype 0:9.Clin Diagn. Lab. Immunol.1996.3:472-476.
[234]Miller. M. J., R. A. Wrightsman. and J. E. Manning.Trypanosoma cruzi:protective immunity in mice immunized with paraflagellar rod proteins is associated with a T-helper type 1 response. Exp. Parasitol.1996,84:156-167.
[235]Victoratos, P., M. Yiangou, N. Avramidis, and l.Hadjipetrou.Regulation of cytokine gene expression by adjuvants in vivo.Clin Exp Immunol.1997,109:569-578.
[236]Araya, L. N., P. H. Elzer, G. H. Rowe, F. M. Enright, and A. J.Winter. Temporal development of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J. Immunol.1989,143:3330-3337.
[237]Araya, L. N., and A. J. Winter.Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum.Infect. Immun.1990,58:254-256.
[238]Cheers, C.Pathogenesis and cellular immunity in experimental murine brucellosis.Dev Biol Stand.1984,56:237-246.
[239]Eze, M. O., L. Yuan, R. M. Crawford, C. M. Paranavitana. T. L. Hadfield, A. K. Bhattacharjee, R. L. Warren, and D. L. Hoover.Effects of opsonization and gamma interferon on growth of Brucella melitensis 16M in mouse peritoneal macrophages in vitro.Infect Immun.2000.68:257-263.
[240]Murphy, E.A., J. Sathiyaseelan, M.A.Parent, B. Zou, and C.L.Baldwin. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice.Immunology.2001.103:511-518.
[241]Zhan, Y., and C. Cheers.Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect. Immun.1993,61:4899-4901.
[242]Cespedes, S., E. Andrews, H. Folch. and A. Onate.Identification and partial characterisation of a new protective antigen of Brucella abortus.J Med Microbiol. 2000,49:165-170.
[243]L.-Y.HUANG,1 A. M. KRIEG,2 N. ELLER,1 AND D. E. SCOTT1.Induction and Regulation of Thl-Inducing Cytokines by Bacterial DNA, Lipopolysacchari de, and Heat-Inactivated Bacteria.Infect. Immun,1999, p.6257-6263.
[244]MosmannTR, SadS.The expanding universe of T-cell subsets:Th1,Th2 and more.[J].Immunol Today.1996.17:138-146.
[245]Emrah Altindis, Burcu E. Tefon.et al. Immunoproteomic analysis of Bordetella pertussis and identification of new immunogenic proteins. Vaccine.2009.27: 542-548.
[246]Amy V Jennison, Rubhana Raqib, Naresh K Verma.Immunoproteome analysis of soluble and membrane proteins of Shigella fl exneri 2457T.World J Gastroenterol.2006,12(41):6683-6688.