Comparative Genome Analysis of Salmonella Species

描述（由申请人提供）： 肠道沙门氏菌有超过 2,000 种已知血清型。这些血清型的宿主范围和致病性差异很大。人类每年因肠道沙门氏菌感染而遭受数千万感染，甚至数十万人死亡。 99% 以上的感染由 I 亚种中的约 100 种血清型引起。迄今为止获得的沙门氏菌基因组序列表明，血清型在存在或不存在数百个基因方面存在差异，这些差异可能是造成宿主范围和致病性的一些差异的原因。该项目将表征作为人类和家畜主要病原体的未测序血清型之间的许多基因差异。在上一个资助期间，我们对迄今为止在已测序的沙门氏菌中鉴定出的几乎所有基因进行了微阵列 PCR 产品。目标 1：新的肠道沙门氏菌基因可用后将被放置在阵列上。目标 2：该阵列将用于探测未测序的肠沙门氏菌 I 亚种基因组，以确定血清型之间基因同源物的分布。目标 3：肠细菌基因组测序揭示了某些位置的多样性“热点”，其中涉及一个或多个基因的插入、删除或替换事件将基因组彼此区分开来。这些差异将通过 PCR 和直接基因组测序来表征未测序的基因组，捕获当前测序的基因组中未发现的一些变异。目标 4：将研究插入/缺失和重排对沙门氏菌基因组高度保守的顺序的影响。在这四个目标中获得的信息将有助于理解沙门氏菌宿主范围和致病性的惊人多样性背后的一些进化机制。这些信息也应该有助于开发流行病学工具，并可能导致沙门氏菌分类学的修订，该分类学目前主要依赖于噬菌体分型和表面抗原的免疫学测量。由于肠沙门氏菌亚种 1 的成员是在使用炭疽之前在美国用于生物恐怖袭击的唯一细菌，因此此类研究具有额外的维度。

DESCRIPTION (provided by applicant): There are over 2,000 known serovars of Salmonella enterica. These serovars differ dramatically in their host range and pathogenicity. Humans suffer tens of millions of infections and perhaps hundreds of thousands of deaths each year from infection by Salmonella enterica. About 100 serovars in subspecies I are responsible for more than 99 percent of these infections. The Salmonella genome sequences obtained, so far, indicate that serovars differ in the presence or absence of many hundreds of genes and these differences are presumably responsible for some of the differences in host range and pathogenicity. This project will characterize many of the gene differences among unsequenced serovars that are major pathogens of humans and domestic animals. In the previous grant period we placed on a microarray PCR products for almost all of the genes identified, so far, in the sequenced Salmonella. Aim 1: New Salmonella enterica genes will be placed on the array as they become available. Aim 2: The array will be used to probe unsequenced Salmonella enterica subspecies I genomes to determine the distribution of gene homologues among serovars. Aim 3: Sequenced enterobacterial genomes reveal "hotspots" of diversity at certain locations where insertion, deletion or replacement events, involving one or more genes, distinguish genomes from each other. These differences will be characterized in unsequenced genomes by PCR and also by direct genome sequencing, capturing some of the variation not found in the currently sequenced genomes. Aim 4: The consequences of insertion/deletion and rearrangement on the otherwise highly conserved order of the Salmonella genome will be studied. The information gained in these four aims will be a step forward in understanding some of the evolutionary mechanisms behind the phenomenal diversity in host-range and pathogenicity of the Salmonella. This information should also be useful in developing tools for epidemiology and could lead to revisions of Salmonella taxonomy, which is currently largely reliant on phage typing and immunological measurements of surface antigens. As a member of S. enterica subspecies 1 was the only bacteria previously used for a bioterror attack in the USA, prior to the use of Anthrax, such studies take on an added dimension.