Apo and Iron Bound Fur Repression and the Role of Fur in vivo

摘要

Helicobacter pylori is a Gram negative neutrophile that persistently colonizes the dynamic gastric environment and is associated with the development of a spectrum of gastric pathology ranging from gastritis to invasive adenocarcinoma. Despite its fluctuating gastric niche, H. pylori genomic studies have revealed surprisingly few regulatory factors and two component systems. Of these identified factors, the Ferric Uptake Regulator (Fur) has been shown to control a diverse regulon. Even though Fur has been identified and characterized in both Gram positive and negative bacteria, to date, H. pylori Fur appears unique in its ability to regulate genes in its apo form. The first section of this study examined the ability of other bacterial Fur to complement apo-Fur regulation in H. pylori. Results from this study showed that Campylobacter jejuni, Desulfovibrio vulgaris, Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae Fur are unable to complement apo- Fur regulation within the context of H. pylori. Next we examined the role of Fur in a gerbil model of infection. The results indicate that Fur is important for establishing colonization and plays a role in the development and progression of disease. The data presented here provide the basis for future studies to examine the role of iron-bound and apo-Fur in vivo. In H. pylori, while Fur is nonessential, it is crucial in the initial colonization and temporal progression and severity of disease.