Our research is focused on the role of essential metal ions in pathogenic bacteria and at the host-pathogen interface. Restriction of a pathogen's access to iron is a well characterised element of the mammalian innate immune system, but there is no reason a priori why such a mechanism of nutritional immunity should be restricted only to iron. Recent data suggest a role for the human protein complex calprotectin in inhibiting growth of Staphylococcus aureus in abscesses through chelation of manganese and/or zinc. In addition to deficiency, metal toxicity can also limit microbial growth. Copper-based Fenton chemistry is used by the immune system to bombard pathogens with reactive oxygen species. Copper salts are used by man as agrochemical fungicides, and silver salts and nanoparticles are increasingly used as antibacterial treatments. Such strategies are likely to gain importance as antibiotic resistance determinants become more widespread among human pathogens.
We use a range of biochemical and biophysical approaches to investigate the mechanisms by which metal depletion or excess give rise to bacterial growth inhibition and death. Such knowledge could in future be exploited by combining non-native metal toxicity with synthetic metal chelators, specific for essential metal ions. Such treatments are likely to be broad-spectrum, due to the essential nature of these metal ions for all life forms. By understanding processes of metal homeostasis in prokaryotes and eukaryotes, we can define the likely benefits of such therapeutic strategies.