Tandemly Repetitive Proteins in Mycoplasmas

支原体中的串联重复蛋白

• 批准号: 7540932
• 负责人: KEVIN F DYBVIG
• 金额: $ 31.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7540932
• 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

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.

支原体通常产生具有相当大的经济影响的疾病，但很少有信息是 关于发病机制和有效的控制方法是不可用的。许多 支原体具有具有相同串联重复区域的表面蛋白，有时具有40个或更多 每个蛋白质的重复单位。这样的分子通常是脂蛋白，其脂质部分用于锚 蛋白质的膜和羧基串联重复区自由地与宿主细胞相互作用， 分子。这些蛋白质都受到高频率的大小变化，由于滑链错配 导致重复单元的增加或减少。这些重复蛋白的功能和表型 尺寸变化的后果是未知的。在鼠病原体肺支原体中， Vsa蛋白调节支原体的生长特性（菌落大小变化），血细胞吸附， 和对补体溶解的敏感性。我们的长期目标是了解 支原体目前的建议的目标是研究的功能和致病意义， Vsa尺寸变化。包括M.肺具有细胞外基质。我们提出 该基质由Vsa蛋白组成，并用于保护支原体免受补体的侵害。 目的1是通过电子显微镜检查基质，以确定其是否由Vsa蛋白组成， 并确定它是否是补体的屏障。Vsa蛋白可能会影响 支原体和宿主细胞，以及Vsa是否调节支原体对 吞噬作用将在目标2中进行检查。在目标3中，Vsa大小变化的致病意义将是 通过比较细胞产生大（许多串联重复）或小（很少重复）的能力来研究 Vsa蛋白在免疫活性细胞和补体系统中定植和致病的能力 缺陷小鼠这些研究的结果将阐明高度重复的蛋白质在支原体感染中的作用。 疾病它们还将提供对其他微生物中重复蛋白质功能的深入了解， 对公共卫生很重要的包括导致疟疾、肺结核和各种细菌的病原体。 肺炎通过了解重复蛋白质在疾病过程中的作用，预计 将制定更好的措施来控制这些重要的人类病原体的感染。