Transferrin maintains free human serum ferric ion concentration at 10-24 M. Pathogenic bacteria compete against this thermodynamic limit through clever coordination chemistry to obtain iron from their human host. It is difficult to overestimate the significance of iron as a limiting nutrient in microbial growth: enhancement of pathogenicity of 4 to 7 orders of magnitude are seen when iron is supplemented. Powerful and selective iron chelators (siderophores) are produced and secreted in response to iron deficiency. These are taken up by membrane transporters. Our studies in this field began 44 years ago and have had continuous NIH support. For the first decade we were the only chemists in the field and the focus was initially on the coordination chemistry of siderophores. The research field and community have grown greatly and spectacular advances have taken place in understanding the recognition and transport processes involved in siderophore-mediated iron acquisition. In recent years siderocalin, a protein of the human innate immune system, has been found to interrupt siderophore mediated iron transport of pathogenic bacteria. Shown below is a picture of human siderocalin with bound, and hence inactivated, ferric enterobactin. Pathogens such as Bacillus anthracis (anthrax) produce “stealth” siderophores that are designed to evade this protein. The production of different types of siderophores correlates with the different life cycles of B. anthracis. Key advances in the field and a summary status report will be presented. A recent review in Accounts of Chemical research has described this odyssey.[1] [1] Kenneth N. Raymond, Benjamin E. Allred, and Allyson K. Sia, “Coordination Chemistry of Microbial Iron Transport,” Acc. Chem. Res. 2015, 48, 2496–2505.

Microbial iron transport: From coordination chemistry to human host competition

251st National Meeting (2016)

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