How is regulation of motility and chemotaxis required for pathogenicity in Helicobacter pylori, specifically for toxin delivery of VacA.

幽门螺杆菌会引起胃炎和胃癌。结果表明，运动调节在致病性中起重要作用。因此，有人认为细菌附着在上皮细胞上依赖于调节的运动性和趋化性来传递毒素。对一种重要的毒素VacA进行了详细的研究，并展示了VacA是如何导致上皮细胞死亡的。在我的研究项目中，我想要调查幽门螺杆菌细胞如何找到它们在上皮细胞或附近的位置来转移VacA毒素，以及为什么趋化性在这一过程中至关重要。为了找出VacA转移与趋化的关系，我将首先分析由趋化引起的致病性是否直接依赖于VacA。为此，我检查了VacA和趋化蛋白是否在一个信号通路中，以及是否可以通过增加VacA的表达来恢复幽门螺杆菌趋化突变株降低的致病性。此外，我想知道幽门螺杆菌细胞是否必须附着在上皮细胞上才能转移VacA毒素，以及附着是否会导致毒素产生的增加。除了在老鼠身上进行的实验外，我还想建立一个新的系统，胃类器官。使用胃有机化合物，我将拥有一个高度可重复性的系统，并将能够最大限度地减少动物试验。为了对趋化性在致病性中的作用有新的见解，我想在共焦显微镜下记录受感染的有机化合物的视频，看看没有趋化性的突变体与野生型相比何时表现不同。

Helicobacter pylori causes gastritis and gastric cancer. It was shown that the regulation of motility plays an important role for the pathogenicity. Therefore, it has been suggested that the bacteria attach to the epithelial cells depending on regulated motility and chemotaxis to deliver toxins. An important toxin, VacA, has been studied in detail and it was shown how VacA causes cell death of epithelial cells. In my research project I want to investigate how H. pylori cells find their position at or in the vicinity of epithelial cells to transfer the toxin VacA and why chemotaxis is crucial for that process. To find the relationship between VacA transfer and chemotaxis, I will first analyze whether the pathogenicity, which is caused by chemotaxis, directly dependents on VacA. For this, I examine whether VacA and chemotaxis proteins are within one signalling pathway, and if I can restore the reduced pathogenicity of H. pylori chemotaxis mutants by increased VacA expression. Furthermore, I want to find out whether H. pylori cells must be attached to epithelial cells to transfer the toxin VacA and whether attachment leads to increased toxin production. In addition to the experiments carried out with mice I want to establish a new system, the gastric organoids. Using gastric organoids I would have a highly reproducable system and will be able to minimize animal testing. To get new insights into the function of chemotaxis for pathogenicity, I want to record videos of the infected organoids under a confocal microscope to see when a mutant without chemotaxis behaves different compared to the wild type.