AN EVOLUTIONARY ANALYSIS OF FIMBRIAE IN ENTEROBACTERIA

描述(改编自申请人摘要)：两名校长 参与这项合作的研究人员提议研究一种 从共生菌到病原菌的选择操作 预先存在的等位基因，而不是通过获得大量的 不同的基因通过水平转移。(后者的一个示例 现象是“致病岛”或带有毒素基因的噬菌体。) 研究人员使用“路径适应”一词来表示选择过程 促进细菌病原体适应的等位基因变异 致病机制的特殊模式。他们建议使用模型系统类型1 大肠埃希菌菌毛和粘附素的进化 用于适应尿路和上呼吸道的粘附素。 在这项研究中，研究人员将收集具有代表性的菌株 并进一步鉴定了菌毛基因及其控制区。 基因。他们将使用单链构象多态和测序 区分不同的变体并确定适应于 人类宿主微环境在调查型研究中的应用。一项前瞻性研究 他们将使用动物模型来验证他们的假设，即 促进动物尿路持久化的菌毛基因将是 被选中，然后在人群中检测到。

DESCRIPTION (Adapted from the Applicant's Abstract): The two principal investigators in this collaboration propose to study the evolution of a bacterium from a commensal to a pathogen through selection operating on pre-existing alleles, rather than through the acquisition of substantially different genes through horizontal transfer. (An example of the latter phenomenon is the "pathogenicity island" or a bacteriophage with a toxin gene.) The investigators use the term "pathoadaption" for the process of selection of allele variants that "promote adaptation of the bacterial pathogens to a particular mode of pathogenesis." They propose to use for a model system type 1 fimbriae and adhesins of Escherichia coli and in particular the evolution of the adhesins for adaptation to the urinary tract and upper respiratory tract. For the study, the investigators will gather together representative strains and further characterize the fimbrial genes and the control regions for the genes. They will use Single Stranded Conformational Polymorphism and sequencing to distinguish the variants and to identify "signatures" for adaptation to the human host microenvironment in a survey type of study. In a prospective study they will use an animal model to test their hypothesis that variant alleles of fimbrial genes that promote persistence in the animal urinary tract will be selected and then detected in the population.