Comparative Genome Analysis of Salmonella Species

描述（由申请人提供）： 已知肠道沙门氏菌有2,000多种血清型。这些血清型在它们的宿主范围和致病性方面有显著差异。人类遭受数以千万计的感染，每年可能有数十万人死于肠道沙门氏菌感染。亚种I中约有100个血清型，占这些感染的99%以上。到目前为止，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差异的原因。该项目将描述人类和家畜的主要病原体未测序血清型之间的许多基因差异。在前一个资助期内，我们将几乎所有的基因都放在了微阵列PCR产物上，到目前为止，在测序的沙门氏菌中。目标1：新的沙门氏菌基因将被放置在阵列上，因为他们变得可用。目标二：该阵列将用于探测未测序的肠道沙门氏菌亚种I基因组，以确定基因同源物在血清型中的分布。目标3：测序的肠细菌基因组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、缺失或替换事件将基因组彼此区分开。这些差异将通过PCR和直接基因组测序在未测序的基因组中进行表征，从而捕获一些在当前测序的基因组中未发现的变异。目的4：将研究沙门氏菌基因组的插入/缺失和重排对高度保守顺序的影响。在这四个目标中获得的信息将是理解沙门氏菌宿主范围和致病性惊人多样性背后的一些进化机制的一步。这些信息也应该是有用的流行病学工具的开发，并可能导致沙门氏菌分类的修订，这是目前主要依赖于噬菌体分型和表面抗原的免疫学测量。作为S.肠杆菌亚种1是美国以前用于生物恐怖袭击的唯一细菌，在使用炭疽之前，这样的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.