Iron is essential - yet toxic both in deficiency and excess. Increasingly the medical literature show that iron plays a key role in areas of human health. The focus of this research project is the essential role iron plays in bacterial growth, and hence the role of iron in human disease caused by bacteria or fungi. The goals are to characterize the mechanisms of siderophore-mediated iron uptake and to understand the role of siderophores in bacterial disease. Previous progress in this on-going project have involved the characterization of several siderophores from human pathogens, the quantitative determination and explanation of the stability or ferric siderophore complexes, the preparation and in vivo use of siderophore analogs, the characterization of the role stereochemistry at the metal center plays in the siderophore recognition and transport process and other aspects of siderophore coordination chemistry. The focus of this proposal now turns in a more microbiological direction. We will study the role of amonabactin in the virulence of Aeromonas hydrophyla, a human pathogen. The ability of this sideophore to remove iron from transferrin will probed and the gene it encodes for an enzyme in the synthesis of amonabactin, amoA, will be isolated to determined the importance of amonabactin in Aeromonas pathogenicity. Recognition and transport of ferric amonabactin will be probed using both four natural siderophores and synthetic analogs. The amonabactin receptor protein will be characterized. The siderophore for the organism that causes whooping cough in humans will be investigated with regard to its kinetic ability to remove iron, and its role in iron uptake will be probed. The latter stages of iron uptake into E.coli. mediated by enterobactin will be probed and the enterobactin esterase will be isolated and characterized. Collaborative studies on siderophores will include their biogeochemistry, marine biochemistry and the characterization of new siderophores.
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