MOLECULAR BASIS OF TYZZER'S DISEASE

TYZZER 病的分子基础

• 批准号: 3478878
• 负责人: LELA K. RILEY
• 金额: $ 8.09万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3478878
• 关键词: autoradiography; bacterial DNA; bacterial disease; diagnosis design /evaluation; diarrhea; enzyme linked immunosorbent assay; gastrointestinal disorder diagnosis; gene expression; gerbil /jird; gram negative bacteria; laboratory mouse; laboratory rabbit; latent bacterial disease; microorganism classification; microorganism culture; molecular cloning; molecular pathology; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; radiotracer; virulence

Tyzzer's disease has been reported in a wide range of laboratory, domestic, and wild animals. Acute infection is characterized by a fatal hemorrhagic enteritis, focal necroses in the liver, and the presence of many intracellular bacilli surrounding the lesions. Acute disease appears to be rare in natural infections, but seemingly healthy animals can harbor a latent form of infection which can develop into acute disease when the animal is subjected to stress. An outbreak of the disease among laboratory animals during the course of an experiment is costly both scientifically and economically. The effects of latent disease on research utilizing infected animals, although potentially significant are not known. Studies of the unclassified etiologic agent, Bacillus piliformis, have been hampered by the difficulties in culturing this obligate intracellular pathogen. The objectives of this proposal include: 1)Biochemical, immunological, and genetic characterization of the causative bacteria to determine the taxonomical classification of the organism and the relatedness of B. piliformis isolates from different host species. 2) Development of improved diagnostic assays using cloned genes and gene products to afford more sensitive, specific, and earlier detection of the disease. 3)Examination of the host:parasite interactions that permit intracellular survival of the pathogen and elucidation of the host response to clinical and asymptomatic disease. For the first time, the experiments designed in this proposal will utilize molecular techniques to examine and probe the causative agent of disease at the genetic level. Moreover, cloning and expression of B. piliformis genes in Escherichia coli will circumvent the limited availability of pathogen components due to the difficulties in culturing the obligate intracellular parasite. These components are needed for the biochemical characterization of the organism and its pathogenesis. The results of these studies will contribute to the basic understanding of Tyzzer's disease, and may potentially yield solutions to the problem of control and prevention of the disease among laboratory animals.

泰泽氏病已经在广泛的实验室中报道， 家养动物和野生动物。急性感染的特征是致命的 出血性肠炎，肝脏局灶性坏死，以及 病变周围有许多胞内杆菌。急性疾病出现 在自然感染中是罕见的，但看似健康的动物可以 潜伏着一种能发展成急性疾病的潜在感染 当动物受到压力时。疾病的爆发， 实验动物在实验过程中是昂贵的， 科学和经济。潜伏性疾病对 利用受感染的动物进行的研究，虽然可能很重要， 不知道。未分类病原体芽孢杆菌的研究 piliformis，一直受到培养这一困难的阻碍， 专性细胞内病原体。 该提案的目标包括：1）生化，免疫， 和致病细菌的遗传特征，以确定 生物体的分类学分类和B的相关性。 piliformis分离物来自不同的宿主物种。2)发展 使用克隆基因和基因产物的改进的诊断测定， 更敏感、更特异、更早地发现疾病。 3)检查宿主：允许细胞内的寄生虫相互作用 病原体的存活和宿主对临床 和无症状的疾病。首次设计了实验 这项建议将利用分子技术来检查和探测 在遗传水平上的致病因素。此外，克隆和 B的表达。大肠杆菌中的piliformis基因将绕过 病原体成分的可用性有限， 培养专性细胞内寄生物。这些组件 所需的生物体的生化表征及其 发病机制这些研究的结果将有助于基本的 了解泰泽病，并可能产生解决方案， 实验室间疾病的控制与预防问题 动物