Peptic ulcer irony

Abstract

Iron is an essential nutrient for all cells, but in the human body, the distribution of iron is tightly controlled. Iron is rapidly sequestered away by transport proteins, such as transferrin and lactoferrin, and stored in intracellular protein complexes (ferritin) and haemoglobin. The resulting very low levels of freely available iron prevent the colonization or infection of the host by many types of bacteria. In response, pathogenic bacteria have evolved complex high-affinity mechanisms for the uptake of nutritional iron in order to survive.Peptic ulcers are thought to be caused by the slow-growing, spiral bacterium Helicobacter pylori. Although 50% of the population are colonized by this organism, clearance of H. pylori from the gut of patients with peptic ulcers is therapeutically beneficial. However, antimicrobial regimes have proved to be complex owing to poor secretion of agents into the gut, inactivation in the acid environment of the stomach and bacterial resistance. Now, Velayudhan et al.1xIron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high-affinity ferrous iron transporter. Velayudhan, J. et al. Mol. Microbiol. 2000; 37: 274–286Crossref | PubMed | Scopus (153)See all References1, using the completed bacterial genome sequence as a guide, have constructed knockout mutants in four genes predicted to be involved in H. pylori iron-uptake pathways. Using this approach, they identified a single gene, feoB, which is necessary for high-affinity uptake of iron. Most importantly, this gene is essential for bacterial colonization of the mouse gut model.The FeoB protein is probably located in the cytoplasmic membrane and relies on an unidentified mechanism to transfer iron from the extracellular environment to the periplasmic space. The FeoB pathway is expressed constitutively, and functions both in iron- restricted and iron-replete conditions. These results not only suggest that uptake of iron by H. pylori is necessary for colonization of the gut, but that surprisingly, this process is dependent on a single protein. This nutritional ‘Achilles heel’ for the bacterium could be a new target for therapies to aid clearance of these organisms, alleviating peptic ulcer discomfort as well as reducing the incidence of gastric carcinoma.