Comparative Genomics in the Enterobateriaceae

描述（由申请人提供）：S。肠道亚种I包含超过1500种不同的血清型，具有非常多样的宿主范围和致病机制。这个持续的项目将产生一个资源的测序基因组和相应的表型数据的明智选择的S。肠道菌血清型来捕获这种多样性。在上一个资助期，测序成本的降低使我们能够完全测序三个肠杆菌基因组，而不是最初提出的两个。测序技术的最新飞跃将允许对另外25个S进行近乎完全的测序。以同样的成本获得基因组。将根据临床和分类学重要性挑选菌株。以前的项目结果告诉我们，沙门氏菌亚种I血清型通常共享约90%的约4500个染色体基因的主链。在这25个菌株中，每个基因组的剩余10%可能含有另外4000个新的或相当不同的基因，包括原噬菌体，其中一些含有多个嵌入的毒力基因。基因组序列将允许前所未有的分辨率在表面标记，如脂多糖和菌毛基因，和横向基因转移事件的加速进化的研究。该项目还将获得96个菌株的宿主范围、毒力和体外表型数据，包括每种测序菌株，以确定研究这些菌株的实验室模型。来自大量S.肠杆菌菌株将公开提供，并将为研究宿主范围、致病机制、新变体的出现奠定基础，并将提供可用于开发新疗法的信息。

DESCRIPTION (provided by applicant): S. enterica subspecies I contains over 1500 different serovars with an extraordinary diversity of host ranges and pathogenic mechanisms. This continuing project will generate a resource of sequenced genomes and corresponding phenotypic data of judiciously chosen S. enterica serovars to capture some of this diversity. In the previous funding period, reductions in sequencing costs allowed us to completely sequence three Enterobacterial genomes instead of the two originally proposed. A recent leap in sequencing technology will allow the near complete sequencing of an additional 25 S. enterica genomes at the same cost. Strains will be picked for both their clinical and their taxonomic importance. Previous project results taught us that Salmonella subspecies I serovars typically share a backbone of about 90% of their -4500 chromosomal genes. The remaining 10% of each genome in these 25 strains may contain an additional 4000 new or considerably divergent genes, including prophage, some of which contain multiple embedded virulence genes. The genome sequences will permit unprecedented resolution in the study of accelerated evolution of surface markers, such as lipolysaccharide and fimbrial genes, and lateral gene transfer events. The project will also acquire data on host-range, virulence, and in vitro phenotypes for 96 strains, including each sequenced strain, to identify laboratory models to study these strains. Sequence, annotation, and phenotypic data from a large number of S. enterica strains will be made publicly available and will lay the groundwork to allow the study of mechanisms responsible for host range, pathogenic mechanism, the emergence of new variants, and will provide information that can be exploited for novel therapy development.