Identification of Salmonella Genes Involved in Persistence in the Murine Intestin

沙门氏菌在小鼠小肠中持续存在的基因鉴定

基本信息

批准号：
7914838
负责人：
HELENE L ANDREWS-POLYMENIS
金额：
$ 42.27万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914838
关键词：
Animal Experiments Animal Feed Animal Model Animals Antibiotics Biological Biological Assay Candidate Disease Gene Cecum Cessation of life Cistrons Clinical Collection Complement Complex Data Development Disadvantaged Disease Dose Epithelium Essential Genes Food Supply Gene Deletion Genes Genetic Genetic Screening Genome Goals Growth Human In Vitro Individual Infection Intestines Lead Libraries Livestock Measures Methods Modeling Molecular Molecular Genetics Monitor Mus Oligonucleotide Microarrays Organism Pathway interactions Phenotype Population Process Proteins Public Health Relative (related person)Resistance Salmonella Salmonella enterica Salmonella infections Salmonella typhimurium Screening procedure Series Serotyping Study models Systemic infection Testing Therapeutic Agents Transcript United States base deletion library fitness foodborne foodborne illness gene function genetic manipulation genome sequencing high throughput screening in vivo mutant new technology novel novel therapeutics oral infection pathogen promoter recombinase tool tool development transmission process vector

项目摘要

We will use the power of complete genome sequences and forward genetics to identify novel genes that allow a bacterial pathogen to colonize and persist in the mammalian intestine. Non-typhoidal Salmonella are food borne bacterial pathogens that cause hundreds of millions of cases of diarrheal disease and hundreds of thousands of deaths worldwide each year. Salmonella enterica serotype Typhimurium is an excellent model for study of intestinal fitness because of the availability of complete genome sequence information, the ease of genetic manipulation, and the availability of numerous animal models. We have generated a collection of 1150 targeted deletion strains (approximately 25% of the genome), developed a novel oligonucleotide microarray, and begun forward genetic screening this mutant collection both in vitro and in vivo in murine and chick models. We wish to complete the development of these tools and progress to more comprehensive studies of a subset of genes involved in intestinal persistence and fecal shedding, processes which are critical for transmission of this organism. We will approach this goal by: 1. Completion of our deletion library in all non-essential genes in Salmonella Typhimurium, 2. Screen our deletion collection in murine models to identify new genes involved in intestinal colonization and persistence, 3. Confirm each mutant as defective for intestinal persistence, 4. Characterize mutants that are defective for intestinal persistence.

我们将利用完整的基因组序列和正向遗传学的力量识别允许细菌病原体定殖并持续存在的新型基因哺乳动物肠。非细类沙门氏菌是食物寄生的细菌导致数亿例腹泻病和每年在全球成千上万的死亡。沙门氏菌肠血清型伤寒是研究肠道适应性的绝佳模型由于完整的基因组序列信息的可用性，因此易于遗传操作以及众多动物模型的可用性。我们已经产生了1150个目标缺失菌株的集合（约25％基因组），开发了一种新型的寡核苷酸微阵列，并开始在体外和鼠体内筛选该突变集合的正向遗传筛查和小鸡模型。我们希望完成这些工具的开发以及进展到对参与基因的一部分的更全面的研究肠道持久性和粪便脱落，对于至关重要的过程这种生物的传播。我们将通过：1。完成此目标我们在鼠伤寒沙门氏菌的所有非必需基因中的缺失库， 2。筛选我们在鼠模型中的删除收集以识别新基因参与肠道定植和持久性，3。确认每个突变体作为肠道持久性有缺陷，4。表征突变体肠道持久性有缺陷。