Comparative Genome Analysis of Salmonella Species

沙门氏菌物种的比较基因组分析

• 批准号: 6617629
• 负责人: MICHAEL MCCLELLAND
• 金额: $ 18.63万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617629
• 关键词: Salmonella; bacterial genetics; enteric bacteria; gene expression; gene mutation; genetic mapping; genome; microarray technology; operon; polymerase chain reaction; virulence

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.

描述(由申请人提供)： 目前已知的肠道沙门氏菌有2,000多个血清型。这些血清型在寄主范围和致病性上有很大的不同。人类每年因感染肠道沙门氏菌而遭受数千万次感染，甚至可能有数十万人死亡。在这些感染中，99%以上是由I亚种的大约100个血清型造成的。到目前为止，获得的沙门氏菌基因组序列表明，不同的血清型存在或不存在数百个基因，这些差异可能是宿主范围和致病性的一些差异的原因。该项目将描述未测序的血清型之间的许多基因差异，这些血清型是人类和家畜的主要病原体。在之前的资助期间，我们在微阵列上放置了到目前为止在已测序的沙门氏菌中识别的几乎所有基因的PCR产物。目标1：新的肠道沙门氏菌基因将被放置在阵列上，当它们变得可用时。目的2：该芯片将用于探测未测序的肠出血性沙门氏菌I亚种基因组，以确定基因同源物在不同血清型之间的分布。目的3：经测序的肠杆菌基因组在涉及一个或多个基因的插入、缺失或替换事件的特定位置显示出多样性的热点，以区分基因组。这些差异将通过聚合酶链式反应和直接基因组测序在未测序的基因组中得到表征，捕捉到一些在目前已测序的基因组中没有发现的变异。目的4：研究插入/缺失和重排对沙门氏菌基因组高度保守序列的影响。在这四个目标中获得的信息将在理解沙门氏菌寄主范围和致病性的惊人多样性背后的一些进化机制方面向前迈进一步。这些信息还应该有助于开发流行病学工具，并可能导致对沙门氏菌分类法的修订，目前沙门氏菌分类法主要依赖于噬菌体分型和表面抗原的免疫学测量。作为肠链球菌亚种1的一员，在使用炭疽菌之前，1是美国唯一用于生物恐怖袭击的细菌，这种研究具有额外的维度。