Control of Flagellation Pattern in Helicobacter pylori

项目摘要/摘要 幽门螺杆菌是消化性溃疡的主要致病因素，也是引起消化性溃疡的主要危险因素。 胃癌和粘膜相关淋巴组织淋巴瘤。幽门螺杆菌细胞使用一簇极鞭毛 运动，这是定植胃上皮所必需的。我们对这些机制的了解 细菌用来调节鞭毛的位置和数量是肤浅的。就像许多极地的情况一样 鞭毛菌，幽门螺杆菌利用GTP酶FlhF和ATPase FlhG控制定位和数量 鞭毛分别为。鸟嘌呤核苷酸交换因子(GEF)促进与GDP结合的 GTP结合形式的许多信号转导GTP酶，但迄今尚未有关于FlhF的全环基金的报道。 幽门螺杆菌flhG下游是一个基因，我们发现它是维持正常鞭毛数量所必需的， 我们将其命名为flhh。我们假设FlhH是FlhF的一个全环。为了了解FlhH的作用，有两个具体的 将追求的目标是：(1)确定FlhH是否刺激FlhF中的鸟核苷酸交换，(2) 确定影响FlhH活性的决定因素或绕过其维持鞭毛数量的要求。这个 拟议的工作将填补我们在幽门螺杆菌和其他细菌如何控制鞭毛数量方面的关键空白。 由于幽门螺杆菌的寄主定植需要能动性，因此从建议的 研究可能导致确定治疗幽门螺杆菌感染的新靶点和策略。

PROJECT SUMMARY/ABSTRACT Helicobacter pylori is the major pathogenic factor for peptic ulcer disease, as well as a major risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. H. pylori cells use a cluster of polar flagella for motility, which is required for colonization of the stomach epithelium. Our knowledge of the mechanisms used by bacteria to regulate the localization and number of flagella is superficial. As is the case in many polar flagellated bacteria, H. pylori uses the GTPase FlhF and the ATPase FlhG to control the localization and number of flagella, respectively. Guanine nucleotide exchange factors (GEFs) facilitate the conversion of GDP-bound to GTP-bound forms of many signal transducing GTPases, but a GEF has not been reported to date for FlhF. Downstream of H. pylori flhG is a gene that we found to be required for maintaining the normal number of flagella, which we designate as flhH. We hypothesize FlhH is a GEF for FlhF. To understand the role of FlhH, two Specific Aims will be pursued: (1) To determine whether FlhH stimulates guanine nucleotide exchange in FlhF, (2) To identify determinants that affect FlhH activity or by-pass its requirement in maintaining flagella number. The proposed work will a fill critical gap in our knowledge of how H. pylori and other bacteria control flagella number. Since motility is required for host colonization by H. pylori, the new information generated from the proposed studies may lead to the identification of new targets and strategies for treatment of H. pylori infections.