幽门螺杆菌是一种寄生在胃粘膜上并能引发B型胃炎、溃疡以及胃癌的革兰氏阴性菌。该细菌合成了一种在细胞内占蛋白总量2%的富含组氨酸的小分量蛋白质Hpn，我们课题组过去的研究工作发现该蛋白是幽门螺杆菌中重要的镍储运蛋白,并且在过量金属离子存在的情况下对细菌的起保护作用；进一步的研究工作发现Hpn能够分泌到幽门螺杆菌体外，在体外形成淀粉样纤维丝，并且对胃上皮细胞产生一定的毒性。本研究课题着眼于研究Hpn是通过何种渠道分泌到幽门螺杆菌体外，我们将利用生物化学和生物物理方法确定Hpn的分泌通道及其与膜的相互作用，并以此为线索深入研究幽门螺杆菌的致病机理，同时这将为新型抗幽门螺杆菌药物的研制提供了一定的启示作用。

Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa of humans and causes type B gastritis, peptic uclerations and gastric carcinoma. Hpn, a histidine-rich protein, is highly abundant (~2% of total proteins synthesized) in this bacterium. Previous work by our group indicated that Hpn is important in nickle storage and metal detoxification. Further work found that Hpn can be secreted by the bacterium and forms amyloid-like fibrils which is cytotoxic to gastric epithelial cells. In this present project, we aim to investigate how Hpn is secreted outside of the bacterium. We will determine the secretion transporter for Hpn as well as the interaction between Hpn and the membrane mimics through the combined use of biochemical and biophysic methods, which will enhance our understanding of the pathology of Helicobacter pylori and will stimulate further the development of new effective anti-Helicobacter prodrugs.