Ferric iron reductases and their contribution to unicellular ferrous iron uptake.

Iron is a necessary element for nearly all forms of life, and the ability to acquire this trace nutrient has been identified as a key virulence factor for the establishment of infection by unicellular pathogens. In the presence of O2, iron typically exists in the ferric (Fe3+) oxidation state, which is highly unstable in aqueous conditions, necessitating its sequestration into cofactors and/or host proteins to remain soluble. To counter this insolubility, and to compete with host sequestration mechanisms, many unicellular pathogens will secrete low molecular weight, high-affinity Fe3+ chelators known as siderophores. Once acquired, unicellular pathogens must liberate the siderophore-bound Fe3+ in order to assimilate this nutrient into metabolic pathways. While these organisms may hydrolyze the siderophore backbone to release the chelated Fe3+, this approach is energetically costly. Instead, iron may be liberated from the Fe3+-siderophore complex through reduction to Fe2+, which produces a lower-affinity form of iron that is highly soluble. This reduction is performed by a class of enzymes known as ferric reductases. Ferric reductases are broadly-distributed electron-transport proteins that are expressed by numerous infectious organisms and are connected to the virulence of unicellular pathogens. Despite this importance, ferric reductases remain poorly understood. This review provides an overview of our current understanding of unicellular ferric reductases (both soluble and membrane-bound), with an emphasis on the important but underappreciated connection between ferric-reductase mediated Fe3+ reduction and the transport of Fe2+ via ferrous iron transporters.

Managing knowledge and technology to foster innovation at the Ohio State University Medical Center.

Biomedical knowledge is expanding at an unprecedented rate-one that is unlikely to slow anytime in the future. While the volume and scope of this new knowledge poses significant organizational challenges, it creates tremendous opportunities to release and direct its power to the service of significant goals. The authors explain how the Center for Knowledge Management at The Ohio State University Medical Center, created during the academic year 2003-04, is doing just that by integrating numerous resource-intensive, technology-based initiatives-including personnel, services and infrastructure, digital repositories, data sets, mobile computing devices, high-tech patient simulators, computerized testing, and interactive multimedia-in a way that enables the center to provide information tailored to the needs of students, faculty and staff on the medical center campus and its surrounding health sciences colleges. The authors discuss how discovering, applying, and sharing new knowledge, information assets, and technologies in this way is a collaborative process. This process creates open-ended opportunities for innovation and a roadmap for working toward seamless integration, synergy, and substantial enhancement of the academic medical center's research, educational, and clinical mission areas.