Control of metabolism of host and pathogen by the Yersinia type three secretion system

在模式生物小肠结肠炎耶尔森菌中，主要引起腹泻的肠杆菌科成员，我们检查了毒力和代谢功能的协调。一种蛋白质运输机制，即所谓的III型分泌系统，允许通过注射效应蛋白来操纵宿主细胞，是致病性耶尔森氏菌最重要的毒力因素之一。我们最近可以证明，III型系统的蛋白质调节病原体的新陈代谢，可能是为了保证III型系统在需要特定代谢条件的感染期间的功能。现在，此外，在第一个资助期间，我们可以显示至少一个额外的III型系统的蛋白质和至少一个额外的代谢酶参与毒力和代谢功能的协调。此外，我们的数据还表明，宿主细胞的新陈代谢也是通过注射III型效应器直接操纵的。我们希望通过代谢流量分析、细胞生物学、生化和结构生物学的方法来扩大我们对第二个资助期病原体和宿主的代谢控制的理解。此外，我们希望这些研究能够为新药的开发做出贡献。

In the model organism Yersinia enterocolitica, a member of the family Enterobacteriaceae primarily causing diarrhoea, we examine the coordination of virulence and metabolic functions. A protein transport machinery, a so-called type III secretion system, which allows to manipulate host cells by injection of effector proteins is among the most important virulence factors of pathogenic Yersinia. We could show recently that proteins of the type III system modulate the metabolism of the pathogen, possibly to guarantee the functionality of the type III system during an infection requiring specific metabolic conditions. Now, in addition, during the first funding period we could show that at least one additional protein of the type III system and at least one additional metabolic enzyme are involved in the coordination of virulence and metabolic functions. Further, our data suggest that also the metabolism of host cells is manipulated directly by the injection of type III effectors. We want to extend our understanding of the metabolic control both of the pathogen and the host in the second funding period by means of metabolic flux analyses, cell biology, biochemical and structural biology methods. We hope that, in addition, these studies can contribute to the development of novel drugs.