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

• 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
• 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

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.

我们将利用完整基因组序列和遗传学的力量， 确定新的基因，允许细菌病原体定殖和坚持在 哺乳动物的肠非伤寒沙门氏菌是食物传播的细菌 导致数亿例疟疾病例的病原体， 全世界每年有成千上万的人死亡。肠道沙门氏菌 鼠伤寒血清型是研究肠道适应性的良好模型 由于完整的基因组序列信息的可用性， 基因操作，以及大量动物模型的可用性。我们 已经产生了1150个靶向缺失菌株的集合（约25%）。 的基因组），开发了一种新的寡核苷酸微阵列，并开始 在体外和小鼠体内对该突变体集合进行正向遗传筛选 和小妞模特。我们希望完成这些工具的开发， 对参与的基因子集进行更全面的研究取得进展， 肠道持久性和粪便脱落，这些过程对于 这种生物的传播。我们将通过以下方式实现这一目标：1。完成 我们在鼠伤寒沙门氏菌中所有非必需基因的缺失文库， 2.在小鼠模型中筛选我们的缺失集合以鉴定新基因 参与肠道定植和持久性，3.确认每个突变体 作为肠持久性缺陷，4.描述突变体， 肠道持久性有缺陷。