Effectors of the Salmonella SPI-2 Type III secretion system

沙门氏菌属是引起多种人类疾病的重要细菌病原体，如胃肠炎和伤寒。沙门氏菌可以侵入宿主细胞并在其中生长，包括专门的白色血细胞（巨噬细胞），其功能是摧毁潜在的病原体。进入宿主细胞后，沙门氏菌驻留在膜囊（空泡）中，并通过它转移大量毒力蛋白。我们知道，这些蛋白质中有几种通过解毒宿主防御和获取营养物质使细菌在液泡内生长。然而，我们所知甚少的其他蛋白质会阻止宿主细胞向其他细胞发送警报信号以引发免疫反应的能力。拟议的研究涉及对这些“抗免疫”毒力蛋白功能的详细调查。一个关键的目标是确定细胞的“目标”，他们必须与干扰主机。为了做到这一点，我们将利用非常强大的现代技术和仪器，可以检测感染细胞非常复杂的环境中非常微小的变化。通过这项研究，我们有可能发现病原体和宿主细胞生物学的新过程，这可能对在我们细胞内繁殖的其他重要病原体产生影响。我们的工作也可能为设计疫苗提供有价值的信息，这些疫苗仍然需要提供有效的长期保护以对抗沙门氏菌和其他细菌病原体。

Salmonella species are important bacterial pathogens causing a variety of human diseases, such as gastroenteritis and typhoid fever. Salmonella can invade and grow inside the cells of its host, including specialised white blood cells (macrophages) whose function is to destroy potential pathogens. Having entered host cells, Salmonella resides within a membranous sac (vacuole), and transfers through it a large number of virulence proteins. We know that several of these proteins enable bacterial growth inside the vacuole by detoxifying host defences and by acquiring nutrients. However other proteins, about which we know very little, block the ability of host cells to send alarm signals to other cells to mount an immune response. The proposed research involves detailed investigations into the functions of these 'anti-immune' virulence proteins. A key objective is to identify the cellular 'targets' with which they must interact to interfere with the host. To do this we will take advantage of very powerful modern techniques and instruments that can detect very small changes in the very complex environment of the infected cell. Through this research we are likely to discover new processes of pathogen and host cell biology, which could have implications for other important pathogens that propagate within our cells. Our work is also likely to provide valuable information for designing vaccines, which are still needed to provide effective long-term protection against Salmonella and other bacterial pathogens.