MOLECULAR GENETIC BASIS OF MYCOPLASMA ANTIGEN VARIATION

这个项目的长期目标是了解分子和 提供可遗传病原菌的系统的遗传学基础 产生表型多样性的能力。分集生成系统 为病原体提供了适应和抵抗的巨大潜力 它们各自的主机环境。由于这些系统通常涉及 单细胞微生物的表面结构，新的表征 表面表型变异的分子基序在 了解微生物适应策略。 有人建议对一种新发现的微生物系统进行表征 涉及新表面结构的抗原性变异。这发生在 猪鼻支原体是一种致病性猪支原体。支原体 由一大群特殊适应的无壁原核生物组成 引起或与动物的几种疾病有关的，包括 天哪。它们似乎与呼吸道、泌尿生殖系统和 其他人类疾病，现在包括获得性免疫缺陷综合症。 猪鼻支原体已经被证明经历了高频阶段。 可变脂蛋白(VLP)表面抗原表达的变异。 结构不同的VLP产品显示非坐标相位变化 和体外可逆的大小变化。生化数据和测序 最近发现的VLP基因显示了一种新的周期结构，在C- 这些高度保守的膜的末端细胞外区- 锚定脂蛋白。建议研究结构和 VLP抗原性和时相变异的分子遗传学基础 理解这种独特的分子适应如何提供这些 有能力产生大范围表面的特殊微生物 多样性。研究这一系统可能会增进我们对全球的了解 微生物适应环境的策略，并可能揭示共同的 几种人和动物支原体病原体使用的策略。贵宾级酒店 具有明确VLP变异的同基因猪鼻分枝杆菌种群的基因 将对结构、大小或表达进行物理映射、排序和 表达以确定基因组组织、结构和 抗原特征、发散和重排介导抗原性或 位相变化。限制性内切酶图谱、克隆、测序和表达 基因组片段的数量将被使用。VLP的可访问表面区 抗原将与突变后的单抗进行映射 重组的VLP产物和VLP基因的转录将被评估 用标准方法在同基因变异体中。

The long range objective of this project is to understand the molecular and genetic basis of systems providing pathogenic bacteria the heritable capability to generate phenotypic diversity. diversity-generating systems provide pathogens an enormous potential for adapting to and withstanding their respective host environments. Since these systems often involve the surface structures on unicellular microbes, characterization of new molecular motifs of surface phenotypic variation is important in understanding microbial strategies for adaptation. It is proposed to characterize a newly-discovered microbial system of antigenic variation involving novel surface structures. This occurs in Mycoplasma hyorhinis, a pathogenic mycoplasma of swine. Mycoplasmas comprise a large group of specially-adapted wall-less procaryotic organisms that cause or are associated with several diseases in animals, including man. They appear to be associated with respiratory, genitourinary and other human disorders, now including acquired immunodeficiency syndrome. Mycoplasma hyorhinis has been shown to undergo high-frequency phase variation in the expression of variable lipoprotein (Vlp) surface antigens. structurally distinct Vlp products display non-coordinate phase variation and reversible size variation in vitro. Biochemical data and sequencing of recently identified vlp genes revealed a novel periodic structure in the C- terminal extracellular region of these otherwise highly conserved membrane- anchored lipoproteins. It is proposed to examine the structural and molecular genetic basis for Vlp antigenic and phase variation in order to understand how this unique molecular adaptation may provide these specialized microbes with the capacity to generate extensive surface diversity. Investigating this system may enhance our global understanding of microbial strategies for environmental adaptation, and may reveal common strategies used by several human and animal mycoplasma pathogens. the vlp genes from isogenic M. hyorhinis populations with defined variations in Vlp structure, size or expression, will be physically mapped, sequenced and expressed in order to determine genomic organization, structural and antigenic features, divergence and rearrangements mediating antigenic or phase variation. Restriction mapping, cloning, sequencing and expression of genomic fragments will be used. Accessible surface regions of Vlp antigens will be mapped with monoclonal antibodies on mutationally altered recombinant Vlp products, and transcription of vlp genes will be assessed in isogenic variants by standard methods.