Metabolism of intracellular Salmonella enterica: One liefstyle in intracellular infections

细胞内肠沙门氏菌的代谢：细胞内感染的一种操作模式

• 批准号: 71840770
• 负责人: Professor Dr. Thomas Dandekar
• 金额: --
• 依托单位: Arbeitsgruppe Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/71840770?language=en
• 关键词: Metabolism; intracellular; Salmonella; enterica; liefstyle

The successful intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole (SCV) in host cells. Based on previous results, metabolic requirements for Salmonella in the SCV shall be characterized further. This includes (i) prediction of intracellular phenotypes of mutant strains based on elementary mode modeling and experimental tests, (ii) isotopolog profiling using 13C compounds in intracellular Salmonella, and (iii) complementation of metabolic defects for attenuated mutant strains. The collaborative work between the Dandekar and Hensel groups proposed for the second funding period should lead to a comprehen-sive understanding of the metabolic requirements of the intracellular lifestyle of Salmonella. Further analyses of intracellular phenotypes will be based on improved elementary modes predictions. Vice versa, based on analyses of mutant phenotypes and isotopolog analyses, iterative refinement of metabolic flux models will be achieved. An ultimate goal will be the comprehensive understanding of the adaptation of Salmonella to the life in a membrane-bound compartment in mammalian cells. Towards an integrated model, comparison of the Salmonella lifestyle with other pathogens and their metabolic requirements during infection, in particular cytoplasmic as for Listeria, or membrane-bound as for Legionella will be made in the context of the priority program.

肠道沙门氏菌成功的细胞内生活方式依赖于宿主细胞中含沙门氏菌的空泡（SCV）内对营养条件的适应。根据先前的结果，应进一步表征SCV中沙门氏菌的代谢要求。这包括（i）基于基本模式建模和实验测试预测突变菌株的细胞内表型，（ii）使用细胞内沙门氏菌中的13 C化合物进行同位素分析，以及（iii）补充减毒突变菌株的代谢缺陷。Dandekar和Hensel小组为第二个资助期提出的合作工作应能全面了解沙门氏菌细胞内生活方式的代谢要求。细胞内表型的进一步分析将基于改进的基本模式预测。反之亦然，基于突变体表型分析和同位素分析，将实现代谢通量模型的迭代细化。最终目标将是全面了解沙门氏菌适应哺乳动物细胞膜结合区室中的生活。为了建立一个综合模型，将在优先计划的背景下，将沙门氏菌的生活方式与其他病原体及其在感染期间的代谢要求进行比较，特别是李斯特菌的细胞质，或军团菌的膜结合。