Dr. Anne Duhme-Klair
University of York

Siderophore Mediated Bacterial Metal Uptake

The health disparities that afflict ethnic and racial minorities, as well as other underserved populations, are not limited to one or two disease categories. They apply to a broad spectrum of disease including infectious diseases. The problem presented by infectious diseases is compounded by the rise of antibiotic resistance strains that in some cases defy treatment with most if not all antibiotics. Infant mortality is augmented by infectious diseases, specially those caused by resistant strains and mortality is also increased in patients that are more susceptible to them as consequence of the presence of another disease such as AIDS, cancer or diabetes.

Siderophores are chelators synthesised by micro-organisms to solubilise iron for uptake into the cell. Siderophores show an enormous affinity and selectivity for different metal ions. They mediate the uptake of iron in micro-organisms, but also affect the transport of other essential metals. They might have a much more general function than has been assumed so far.

The objectives of this project are to determine the key structural features of the siderophores produced by the N₂-fixing cells of Azotobacter vinelandii that lead to their discrimination between Fe(III) and Mo(VI) and to define the role of stereoselectivity and enantioselectivity in this process. The formulation of a general structure-function relationship is highly relevant to the design of specific metal chelators of potential pharmacological interest. The study may lead to specific sensing applications and to a better understanding of the chemistry underlying the initial biological transformations of Fe and Mo in N₂-fixing bacteria.

Techniques involved:

Synthesis of siderophores involving amide bond formations; UV, fluorescence and CD spectroscopy; HPLC.

Background of the student:

Some experience in synthetic chemistry and knowledge of basic microbiological techniques would be of advantage.