Adaptive evolution of pathogenesis towards symbiosis

发病机制向共生的适应性进化

• 批准号: 6704374
• 负责人: Serap AKSOY
• 金额: $ 26.08万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6704374
• 关键词: Glossinidae; biochemical evolution; developmental genetics; fluorescent in situ hybridization; functional /structural genomics; gene environment interaction; gene expression; gene expression profiling; genetic transcription; host organism interaction; intermolecular interaction; light microscopy; microarray technology; microorganism genetics; microorganism interaction; parasitism; pathologic process; polymerase chain reaction; symbiosis

DESCRIPTION (provided by the applicant): Symbiotic microbial relations are extremely pervasive, with examples being found among all levels of the earth's biota. These associations vary with regard to their interactive nature, and are characterized by the benefit (or detriment) imparted to the participants. Beneficial/neutral symbiotic associations are believed to have evolved from free living or parasitic ancestors. Closely related members of taxa can represent all trophic levels: from free-living to parasitic to mutualistic. Analysis of the genetic differences/similarities between these organisms, in reference to their symbiotic status, can provide important insight into the fundamental biological principles involved in shaping these particular relationships. Tsetse flies are the sole vectors of African trypanosomes, (Trypanosoma spp.), eukaryotic parasites that cause devastating diseases in humans and animals in Sub Saharan Africa. Since tsetse harbors three bacterial symbionts in addition to the protozoan trypanosomes, they provide an ideal model for studying symbiotic associations and interactions. Two of these bacterial symbionts (genus Wigglesworthia and genus Sodalis) are of particular research interest since they are closely related to important free-living and pathogenic bacteria of the Enterobacteriaceae. The genomes of Wigglesworthia, Sodalis and Trypanosoma spp. have been sequenced, which will facilitate in observing symbiosis at the genetic and functional level. Information on the interaction of tsetse symbionts with each other, with trypanosomes and with the host can be applied to other symbiotic systems (i.e., host-pathogen interactions). This study focuses on the genomic and functional biology of symbiosis in tsetse, in an attempt to understand how host factors/environment influence the architecture of microbial genomes during the evolutionary transition from free-living to symbiotic. This will be accomplished by examining functional biology of symbionts (by gene expression profiling) under different host nutritional states, developmental stages and varied parasite infection status. The role of functions typically associated with pathogenic microorganisms will be pursued in these beneficial microbes.

描述（由申请人提供）：共生微生物关系非常普遍，在地球生物群的所有层次中都有实例。这些协会的互动性质各不相同，其特点是对参与者有利（或有害）。有益/中性共生协会被认为是从自由生活或寄生的祖先进化而来的。分类群中密切相关的成员可以代表所有 营养层次：从自由生活到寄生再到互利共生。分析这些生物体之间的遗传差异/相似性，参考它们的共生状态，可以提供重要的洞察力，以形成这些特定关系所涉及的基本生物学原理。 采采蝇是非洲锥虫（锥虫属）的唯一媒介，在撒哈拉以南非洲，真核寄生虫会给人类和动物带来毁灭性的疾病。由于采采蝇除了原生动物锥虫外还含有三种细菌共生体，它们为研究共生关系和相互作用提供了理想的模型。其中两种细菌共生体（属Wigglesophagia和属Sodalis）是特别的研究兴趣，因为它们是密切相关的重要的自由生活和致病性细菌的肠杆菌科。本文报道了三种锥虫的基因组。已经测序，这将有助于在遗传和功能水平上观察共生。关于采采蝇共生体彼此之间、与锥虫以及与宿主之间相互作用的信息可以应用于其他共生系统（即，宿主-病原体相互作用）。本研究的重点是采采蝇共生的基因组和功能生物学，试图了解宿主因素/环境如何影响微生物基因组的结构，从自由生活到共生的进化过渡。这将通过研究不同宿主营养状态、发育阶段和不同寄生虫感染状态下共生体的功能生物学（通过基因表达谱）来实现。将在这些有益微生物中追求通常与病原微生物相关的功能的作用。