Control of Flagellation Pattern in Helicobacter pylori

项目总结/摘要 幽门螺杆菌是消化性溃疡的主要致病因素，也是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。H.幽门螺杆菌细胞使用一簇极鞭毛 用于胃上皮定植所需的运动性。我们对这些机制的了解 细菌用来调节鞭毛的定位和数量的基因是肤浅的。在许多极地地区， 鞭毛菌、H. pylori使用GT3 FlhF和ATP酶FlhG来控制定位和数量 的鞭毛。鸟嘌呤核苷酸交换因子（GEF）促进GDP结合的转化为 许多信号转导GTP酶的GTP结合形式，但迄今尚未报道FlhF的GEF。 下游H。幽门螺杆菌flhG是我们发现维持鞭毛正常数量所需的基因， 我们将其命名为flhH。我们假设FlhH是FlhF的GEF。为了了解FlhH的作用，两个特定的 目的是：（1）确定FlhH是否刺激FlhF中的鸟嘌呤核苷酸交换，（2） 鉴定影响FlhH活性或绕过其维持鞭毛数量要求的决定因素。的 所提出的工作将填补我们对H.幽门螺杆菌和其他细菌控制鞭毛的数量。 由于运动性是H.幽门螺杆菌，新的信息产生的建议， 这些研究可能会导致确定新的目标和治疗H的策略。幽门感染

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.