BACTERIAL GENETICS MOLECULAR PATHOGENESIS OF SALMONELLA

沙门氏菌的细菌遗传学分子发病机制

• 批准号: 3085283
• 负责人: Samuel I Miller
• 金额: $ 8.74万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085283
• 关键词: Salmonella infections; Salmonella typhimurium; Salmonella vaccines; acid phosphatase; antiinfective agents; bacterial antigens; genetic manipulation; immunological substance; laboratory mouse; live vaccine; molecular pathology; mutant; nucleic acid sequence; typhoids; virulence

I plan to study the pathogenesis of Salmonella infections using classical and molecular genetics. My long term goal is the development of a live Salmonella vaccine that can be used as a carrier to deliver heterologous antigens to the immune system. Phase I of this grant includes formal coursework in basic science necessary to study pathogenic bacteria and develop live attenuated bacterial vaccines. Phase I research training will be spent in the laboratory of Dr. John Mekalanos studying the molecular pathogenesis of Salmonella infections. Our preliminary investigations demonstrate that Salmonella typhimurium mutants deficient in the gene regulating acid phosphatase production (phoP) have reduced virulence in a mouse model of typhoid fever. We plan to investigate the cause of this reduced virulence. We also plan to identify S. typhimurium genes important to virulence by the use of several techniques including transposon mutagenesis to create gene translational fusions to E. coli alkaline phosphatase. We also plan to develop a vector delivery system for rapid and stable insertion of genes encoding heterologous antigens on the Salmonella chromosome.

我计划使用经典研究沙门氏菌感染的发病机理 和分子遗传学。 我的长期目标是开发现场 可以用作携带异源的携带者的沙门氏菌疫苗 免疫系统的抗原。 这笔赠款的第一阶段包括必要的基础科学课程 研究病原菌并发展出活的细菌 疫苗。 第一阶段的研究培训将用于博士的实验室。 约翰·梅卡拉诺斯（John Mekalanos）研究沙门氏菌的分子发病机理 感染。 我们的初步调查表明沙门氏菌 鼠伤寒突变体缺乏调节酸磷酸酶的基因 生产（PHOP）在伤寒小鼠模型中的毒力降低。 我们计划研究这种毒力降低的原因。 我们也计划 鉴定鼠伤寒链霉基因对毒力很重要 几种包括转座子诱变的技术以创建基因 转化为大肠杆菌碱性磷酸酶。 我们还计划 开发一个矢量输送系统，以快速稳定的基因插入 在沙门氏菌染色体上编码异源抗原。