Dr Kevin Waldron
University Research Fellow
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 7369
- Fax: +44 (0) 191 208 7424
- Address: Institute for Cell and Molecular Biosciences
Catherine Cookson Building
Newcastle upon Tyne
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.
- He D, Hughes S, Vanden-Hehir S, Georgiev A, Altenbach K, Tarrant E, Mackay CL, Waldron KJ, Clarke DJ, Marles-Wright J. Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments. eLife 2016, 5, e18972.
- Ikeh MA, Kastora SL, Day AM, Herrero-de-Dios CM, Tarrant E, Waldron KJ, Banks AP, Bain JM, Lydall D, Veal EA, MacCallum DM, Erwig LP, Brown AJ, Quinn J. Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis. Molecular Biology of the Cell 2016, 27(17), 2784-2801.
- Abellón-Ruiz J, Waldron KJ, Connolly BA. Archaeoglobus Fulgidus DNA Polymerase D: A Zinc-Binding Protein Inhibited by Hypoxanthine and Uracil. Journal of Molecular Biology 2016, 428(14), 2805-2813.
- Vita N, Platsaki S, Basle A, Allen SJ, Paterson NG, Crombie AT, Murrell JC, Waldron KJ, Dennison C. A four-helix bundle stores copper for methane oxidation. Nature 2015, 525(7567), 140-143.
- Singh A, Panting RJ, Varma A, Saijo T, Waldron KJ, Jong A, Ngamskurungroj P, Chang YC, Rutherford JC, Kwon-Chung KJ. Factors required for Activation of Urease as a Virulence Determinant in Cryptococcus neoformans. mBio 2013, 4(3), e00220-13.
- Tu WY, Pohl S, Gray J, Robinson NJ, Harwood CR, Waldron KJ. Cellular Iron Distribution in Bacillus anthracis. Journal of Bacteriology 2012, 194(5), 932-940.
- Tottey S, Patterson CJ, Banci L, Bertini I, Felli IC, Pavelkova A, Dainty SJ, Pernil R, Waldron KJ, Foster AW, Robinson NJ. Cyanobacterial metallochaperone inhibits deleterious side reactions of copper. Proceedings of the National Academy of Sciences 2012, 109(1), 95-100.
- Waldron KJ, Firbank SJ, Dainty SJ, Pérez-Rama M, Tottey S, Robinson NJ. Structure and Metal Loading of a Soluble Periplasm Cuproprotein. Journal of Biological Chemistry 2010, 285(42), 32504-32511.
- Osman D, Waldron KJ, Denton H, Taylor CM, Grant AJ, Mastroeni P, Robinson NJ, Cavet JS. Copper Homeostasis in Salmonella Is Atypical and Copper-CueP Is a Major Periplasmic Metal Complex. Journal of Biological Chemistry 2010, 285(33), 25259-25268.
- Waldron KJ, Robinson NJ. How do bacterial cells ensure that metalloproteins get the correct metal?. Nature Reviews Microbiology 2009, 7(1), 25-35.
- Waldron KJ, Rutherford JC, Ford D, Robinson NJ. Metalloproteins and metal sensing. Nature 2009, 460(7257), 823-830.
- Tottey S, Waldron KJ, Firbank SJ, Reale B, Bessant C, Sato K, Cheek TR, Gray J, Banfield MJ, Dennison C, Robinson NJ. Protein-folding location can regulate manganese-binding versus copper- or zinc-binding. Nature 2008, 455(7216), 1138-1142.
- Waldron KJ, Tottey S, Yanagisawa S, Dennison C, Robinson NJ. A periplasmic iron-binding protein contributes toward inward copper supply. Journal of Biological Chemistry 2007, 282(6), 3837-3846.
- Angeletti B, Waldron KJ, Freeman KB, Bawagan H, Hussain I, Miller CCJ, Lau K-F, Tennan ME, Dennison C, Robinson NJ, Dingwall C. BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper. Journal of Biological Chemistry 2005, 280(18), 17930-17937.
- Garcia YM, Barwinska-Sendra A, Tarrant E, Skaar EP, Waldron KJ, Kehl-Fie TE. A Superoxide Dismutase Capable of Functioning with Iron or Manganese Promotes the Resistance of Staphylococcus aureus to Calprotectin and Nutritional Immunity. PLoS Pathogens 2017, 13(1), e1006125.
- Barwinska-Sendra A, Waldron KJ. The Role of Intermetal Competition and Mis-Metalation in Metal Toxicity. In: Robert K. Poole, ed. Microbiology of Metal Ions. Kidlington, Oxford: Academic Press, 2017, pp.315-379.
- Vita N, Landolfi G, Basle A, Platsaki S, Lee J, Waldron KJ, Dennison C. Bacterial cytosolic proteins with a high capacity for Cu(I) that protect against copper toxicity. Scientific Reports 2016, 6, 39065.