结核分枝杆菌黏附素HBHA的制备及其应用研究
发布时间：2019-04-12 20:23
【摘要】：研究背景 结核病仍严重威胁人类健康,是单一致病菌致死率最高的疾病。目前,传统的细菌学检测方法需时较长,阳性率较低,在结核病特别是肺外结核诊断上仍然存在许多问题。耐药结核分枝杆菌的流行以及抗结核药物的相对落后对现有的治疗措施提出了挑战。全球唯一使用的预防结核病疫苗-卡介苗也不能有效地预防最常见的成人肺结核的发生。因此,寻求新的诊断、预防和治疗方法在结核病防治工作中是十分重要的。 肝素结合血凝素(heparin-binding haemagglutinin, HBHA)是结核分枝杆菌分泌的一种黏附素,在肺外播散性结核的发生中是一种重要的毒力因素。结核分枝杆菌黏附素的研究目前主要集中于黏附素与宿主细胞相互关系及其生物学特性方面的研究,在结核病免疫诊断、治疗和预防方面的应用研究刚刚起步,国内这方面仍是空白,其它细菌黏附素的研究也很少。阐明结核分枝杆菌黏附素HBHA在结核病免疫应答中的作用,探索其在结核病诊断、预防和治疗等方面的应用,对于结核病防治工作中是十分重要的。 研究目的和方法 1 扩增选择菌株的16S rDNA序列及hbhA编码基因的特异片段,观察结核分枝杆菌、非结核分枝杆菌标准株、肺结核病人和肺外结核病人临床分离株是否存在hbhA基因的缺失。 2 应用克隆表达技术及亲和层析技术分别从大肠杆菌和结核分枝杆菌培养滤液中分离纯化结核分枝杆菌黏附素HBHA蛋白,以HBHA免疫小鼠观察抗HBHA抗体的产生并探讨其免疫原性。 3 研究结核分枝杆菌黏附素HBHA在结核病血清学诊断中的价值,明确HBHA是否具有免疫预防和治疗作用。 研究结果
[Abstract]:Background Tuberculosis is still a serious threat to human health and the highest mortality rate of single pathogen. At present, traditional bacteriological detection methods take a long time, and the positive rate is low. There are still many problems in the diagnosis of tuberculosis, especially extrapulmonary tuberculosis. The prevalence of drug-resistant Mycobacterium tuberculosis and the relative backwardness of anti-tuberculosis drugs challenge the existing treatment measures. Nor does BCG, the world's only vaccine against TB, effectively prevent the most common adult TB. Therefore, the search for new diagnosis, prevention and treatment is very important in tuberculosis prevention and treatment. Heparin-binding hemagglutinin (heparin-binding haemagglutinin, HBHA), an adhesin secreted by Mycobacterium tuberculosis, is an important virulence factor in the development of extrapulmonary disseminated tuberculosis. At present, the research of Mycobacterium tuberculosis adhesin mainly focuses on the relationship between adhesin and host cells and its biological characteristics, and the application of adhesin in the immunodiagnosis, treatment and prevention of tuberculosis has just started. Domestic this aspect is still blank, other bacterial adhesin research is also very few. To clarify the role of Mycobacterium tuberculosis adhesin HBHA in the immune response of tuberculosis and to explore its application in the diagnosis prevention and treatment of tuberculosis is very important for the prevention and treatment of tuberculosis. Objective and methods 1 to amplify the 16s rDNA sequence and the specific fragment of hbhA coding gene of the selected strain, and to observe the standard strains of Mycobacterium tuberculosis and non-tuberculous mycobacterium. Whether there is a deletion of hbhA gene in clinical isolates of pulmonary tuberculosis patients and extrapulmonary tuberculosis patients. 2Clone expression technique and affinity chromatography were used to isolate and purify Mycobacterium tuberculosis adhesin HBHA protein from Escherichia coli and Mycobacterium tuberculosis culture filtrate respectively. The production and immunogenicity of anti-HBHA antibody were observed in mice immunized with HBHA. (3) to study the value of Mycobacterium tuberculosis adhesin HBHA in the serological diagnosis of tuberculosis, and to determine whether HBHA has immunoprophylactic and therapeutic effects. Research results
【学位授予单位】：北京市结核病胸部肿瘤研究所
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R378
本文编号：2457364
[Abstract]:Background Tuberculosis is still a serious threat to human health and the highest mortality rate of single pathogen. At present, traditional bacteriological detection methods take a long time, and the positive rate is low. There are still many problems in the diagnosis of tuberculosis, especially extrapulmonary tuberculosis. The prevalence of drug-resistant Mycobacterium tuberculosis and the relative backwardness of anti-tuberculosis drugs challenge the existing treatment measures. Nor does BCG, the world's only vaccine against TB, effectively prevent the most common adult TB. Therefore, the search for new diagnosis, prevention and treatment is very important in tuberculosis prevention and treatment. Heparin-binding hemagglutinin (heparin-binding haemagglutinin, HBHA), an adhesin secreted by Mycobacterium tuberculosis, is an important virulence factor in the development of extrapulmonary disseminated tuberculosis. At present, the research of Mycobacterium tuberculosis adhesin mainly focuses on the relationship between adhesin and host cells and its biological characteristics, and the application of adhesin in the immunodiagnosis, treatment and prevention of tuberculosis has just started. Domestic this aspect is still blank, other bacterial adhesin research is also very few. To clarify the role of Mycobacterium tuberculosis adhesin HBHA in the immune response of tuberculosis and to explore its application in the diagnosis prevention and treatment of tuberculosis is very important for the prevention and treatment of tuberculosis. Objective and methods 1 to amplify the 16s rDNA sequence and the specific fragment of hbhA coding gene of the selected strain, and to observe the standard strains of Mycobacterium tuberculosis and non-tuberculous mycobacterium. Whether there is a deletion of hbhA gene in clinical isolates of pulmonary tuberculosis patients and extrapulmonary tuberculosis patients. 2Clone expression technique and affinity chromatography were used to isolate and purify Mycobacterium tuberculosis adhesin HBHA protein from Escherichia coli and Mycobacterium tuberculosis culture filtrate respectively. The production and immunogenicity of anti-HBHA antibody were observed in mice immunized with HBHA. (3) to study the value of Mycobacterium tuberculosis adhesin HBHA in the serological diagnosis of tuberculosis, and to determine whether HBHA has immunoprophylactic and therapeutic effects. Research results
【学位授予单位】：北京市结核病胸部肿瘤研究所
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R378
【引证文献】
相关博士学位论文 前1条
1 葛淑敏;非结核分枝杆菌的鉴定及胞内分枝杆菌HBHA表达和实验免疫研究[D];吉林农业大学;2013年
，本文编号：2457364
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