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Tandemly Repetitive Proteins in Mycoplasmas

支原体中的串联重复蛋白

基本信息

批准号：
7740176
负责人：
KEVIN F DYBVIG
金额：
$ 30.87万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-12-15 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7740176
关键词：
Affect Alveolar Macrophages Antigens Bacterial Pneumonia C-terminal Cell Wall Cell surface Cells Complement Complement Component Protein Complement Membrane Attack Complex Complex Cytolysis Deposition Digestion Disease Distal Electron Microscopy Enzymes Extracellular Matrix Family Family member Frequencies Gene Family Genes Genetic Variation Genome Goals Growth Hemadsorption Human Immunocompetent Individual Infection Control Label Length Lesion Lipids Lipoproteins Lung Lung diseases Malaria Manuscripts Measures Membrane Membrane Proteins Methods Microbe Modeling Modification Mus Mycoplasma Mycoplasma pulmonis Organelles Parasites Pathogenesis Phagocytosis Phase Predisposition Process Production Property Proteins Public Health Radiolabeled Rattus Relative (related person)Research Personnel Resistance Role Severities Site Sodium Chloride Solutions Structure Study models Surface Surface Antigens System Tandem Repeat Sequences Thick Trypsin Tuberculosis Variant Virulence capsule cell type complement C3 precursor economic impact extracellular improved insight member microbial pathogen programs radiotracer resistant strain respiratory

项目摘要

Mycoplasmas commonly produce diseases of considerable economic impact, yet little information is available concerning mechanisms of pathogenesis and effective methods of control are unavailable. Many mycoplasmas possess surface proteins with regions of identical tandem repeats, sometimes with 40 or more repeat units per protein. Such molecules are usually lipoproteins with the lipid moiety serving to anchor the protein to the membrane and the carboxyl tandem repeat region free to interact with host cells and molecules. These proteins are all subject to high-frequency size variation due to slipped-strand mispairing that result in gain or loss of repeat units. The functions of these repetitive proteins and the phenotypic consequences of size variation are unknown. In the murine pathogen Mycoplasma pulmonis, size variation in the Vsa proteins modulates the growth properties of the mycoplasma (colony size variation), hemadsorption, and susceptibility to complement lysis. Our long-range goals are to understand the pathogenic mechanisms of mycoplasmas. The goal of the current proposal is to study the functions and pathogenic significance of Vsa size variation. Many mycoplasmas including M. pulmonis possess an extracellular matrix. We propose that this matrix is composed of the Vsa proteins and serves to protect the mycoplasma from complement. Aim 1 is to examine the matrix by electron microscopy,to determine if it is composed of the Vsa proteins, and to determine whether it is a barrier to complement. The Vsa proteins may affect interactions between the mycoplasma and host cells, and whether Vsa modulates the susceptibility of the mycoplasma to phagocytosis will be examined in Aim 2. In Aim 3, the pathogenic significance of Vsa size variation will be studied by comparing the ability of cells that produce a large (many tandem repeats) or a small (few repeats) Vsa protein in respect to their ability to colonize and cause disease in immuno-competent and complement- deficient mice. The results of these studies will elucidate the role of highly repetitive proteins in mycoplasmal diseases. They will also provide insight into the functions of repetitive proteins in other microbes that are important to public health including the agents responsible for malaria, tuberculosis, and a variety of bacterial pneumonias. By understanding the role of repetitive proteins in the disease process, it is anticipated that improved measures to control the infections of these significant human pathogens will be developed.

支原体通常会产生相当大的经济影响的疾病，但很少有信息表明目前尚无关于其发病机制的现有文献和有效的防治方法。许多支原体的表面蛋白具有相同的串联重复序列区域，有时有40个或更多每种蛋白质的重复单位。这种分子通常是脂蛋白，其脂部分起到锚定蛋白质到膜和羧基串联重复区域，自由与宿主细胞相互作用和分子。由于滑链错配，这些蛋白质都受到高频大小变化的影响这会导致重复单位的收益或损失。这些重复蛋白的功能和表型大小变化的后果尚不清楚。在小鼠病原体肺支原体中，大小变异 VSA蛋白调节支原体的生长特性(菌落大小变化)、血液吸附、以及对补体溶解的易感性。我们的长期目标是了解致病机制支原体。目前的建议的目的是研究血管内皮细胞的功能和致病意义。 VSA大小变异。包括肺支原体在内的许多支原体都具有细胞外基质。我们建议这种基质由VSA蛋白组成，起到保护支原体免受补体的作用。目的1是用电子显微镜检查基质，确定它是否由VSA蛋白组成，并确定它是否是补充的障碍。VSA蛋白可能影响细胞间的相互作用支原体和宿主细胞，以及VSA是否调节支原体对在目标2中将检查吞噬作用。在目标3中，VSA大小变异的致病意义将是通过比较产生大的(许多串联重复)或小的(几个重复)的细胞的能力来研究 VSA蛋白在免疫活性和补体中的定植和致病能力- 有缺陷的小鼠。这些研究的结果将阐明高重复蛋白在支原体中的作用。疾病。他们还将提供对重复蛋白在其他微生物中的功能的洞察对公众健康很重要，包括导致疟疾、结核病和各种细菌的病原体肺炎。通过了解重复蛋白在疾病过程中的作用，预计将制定改进的措施来控制这些重要的人类病原体的感染。