Control of Flagellation Pattern in Helicobacter pylori

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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.