Background

Principal Research Fellow, Institute for Cell & Molecular Biosciences (2018-Present).

Wellcome Trust/Royal Society Sir Henry Dale Fellow, Newcastle University (2013-8).

Faculty Fellow, Faculty of Medical Sciences, Newcastle University (2010-2013).

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Arturo Leone Young Investigator prize winner 2018.

Guest Professor:- Nanjing Agricultural University, People's Republic of China (2019-Present).

Research

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 d-block metals, which are essential micronutrients, is an important mechanism by which the immune system controls the proliferation of invading pathogenic microorganisms, known as 'nutritional immunity'. Some metals, such as copper and zinc, can also be extremely toxic to bacteria in excess, and this metal toxicity can also be exploited by the immune system to kill pathogens. Copper alloys and salts have a long history of use 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.

Teaching

Medical Sciences MRes Programmes, Administration Team member.

Lecturer: UG Biochemistry, MRes (Molecular Microbiology, Research Methods in Protein Science).

Publications

• Barwinska-Sendra A, Garcia YM, Sendra KM, Baslé A, Mackenzie ES, Tarrant E, Card P, Tabares LC, Bicep C, Un S, Kehl-Fie TE, Waldron KJ. An evolutionary path to altered cofactor specificity in a metalloenzyme. Nature Communications 2020, 11(1), 2738.
• Giachino A, Waldron KJ. Copper tolerance in bacteria requires the activation of multiple accessory pathways. Molecular Microbiology 2020, 114(3), 377-390.
• Malyar RM, Naseri E, Li H, Ali I, Farid RA, Liu D, Maroof K, Nasim M, Banuree SAH, Huang K, Waldron KJ, Chen X. Hepatoprotective Effects of Selenium-Enriched Probiotics Supplementation on Heat-Stressed Wistar Rat Through Anti-Inflammatory and Antioxidant Effects. Biological Trace Element Research 2021, 199, 3445-3456.
• Piergentili C, Ross J, He D, Gallagher KJ, Stanley WA, Adam L, Mackay CL, Baslé A, Waldron KJ, Clarke DJ, Marles-Wright J. Dissecting the structural and functional roles of a putative metal entry site in encapsulated ferritins. Journal of Biological Chemistry 2020, 295, 15511-15526.
• Ross J, Lambert T, Piergentili C, He D, Waldron KJ, Mackay CL, Marles-Wright J, Clarke DJ. Mass spectrometry reveals the assembly pathway of encapsulated ferritins and highlights a dynamic ferroxidase interface. Chemical Communications 2020, 56(23), 3417-3420.
• He D, Piergentili C, Ross J, Tarrant E, Tuck LR, Mackay CL, McIver Z, Waldron KJ, Clarke DJ, Marles-Wright J. Conservation of the structural and functional architecture of encapsulated ferritins in bacteria and archaea. Biochemical Journal 2019, 476(6), 975-989.
• Tarrant E, Riboldi GP, McIlvin MR, Stevenson J, Barwinska-Sendra A, Stewart LJ, Saitob MA, Waldron KJ. Copper stress in Staphylococcus aureus leads to adaptive changes in central carbon metabolism. Metallomics 2019, 11(1), 183-200.
• Stewart LJ, Thaqi D, Kobe B, McEwan AG, Waldron KJ, Djoko KY. Handling of nutrient copper in the bacterial envelope. Metallomics 2019, 11(1), 50-63.
• Zapotoczna M, Riboldi GP, Moustafa AM, Dickson E, Narechania A, Morrissey JA, Planet PJ, Holden MTG, Waldron KJ, Geoghegan JA. Mobile-Genetic-Element-Encoded Hypertolerance to Copper Protects Staphylococcus aureus from Killing by Host Phagocytes. mBio 2018, 9(5).
• Purves J, Thomas J, Riboldi GP, Zapotoczna M, Tarrant E, Andrew PW, Londono A, Planet PJ, Geoghegan JA, Waldron KJ, Morrissey JA. A horizontally gene transferred copper resistance locus confers hyper‐resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages. Environmental Microbiology 2018, 20(4), 1576-1589.
• Barwinska-Sendra A, Basle A, Waldron KJ, Un S. A charge polarization model for the metal-specific activity of superoxide dismutases. Physical Chemistry Chemical Physics 2018, 20(4), 2363-2372.
• 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.
• 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.
• 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.
• 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.