Staff profile
Affiliation |
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Associate Professor in the Department of Biosciences |
Visiting Assistant Professor in the Department of Chemistry |
Biography
Research Program
Trace nutrient metal ions (iron, manganese, zinc, copper) are essential for the function of nearly half of all proteins but they are toxic to cells if present in excess or if inserted into the wrong sites. The battle to control metal availability is now recognised as a key component of host-pathogen interactions in so-called “Nutritional Immunity” and there is growing interest in developing agents that manipulate nutrient metal level and location as new antimicrobial therapeutics.
Key questions that drive our research program are:
1. How does host-imposed, metal-linked nutritional immunity impact bacterial physiology?
2. How do bacteria adapt to the effects of nutritional immunity?
3. When/where in the host do bacterial pathogens encounter metal ions?
4. Can we learn from nature and manipulate metal levels and locations as new antibacterial approaches?
Research interests
- Metals in microbiology
- Infectious diseases
- Microbial physiology
- Antimicrobial resistance
- Antimicrobial development
Publications
Chapter in book
- Turner, A. G., Ong, C.-L. Y., Walker, M. J., Djoko, K. Y., & McEwan, A. G. (2017). Transition Metal Homeostasis in Streptococcus pyogenes and Streptococcus pneumoniae. In Microbiology of Metal Ions (123-191). https://doi.org/10.1016/bs.ampbs.2017.01.002
- Djoko, K. Y., Achard, M. E., & McEwan, A. G. (2013). Copper in Immune Cells. In Encyclopedia of Inorganic and Bioinorganic Chemistry (1-11). https://doi.org/10.1002/9781119951438.eibc2145
- McEwan, A. G., Djoko, K. Y., Chen, N. H., Couñago, R. L., Kidd, S. P., Potter, A. J., & Jennings, M. P. (2011). Novel Bacterial MerR-Like Regulators: Their Role in the Response to Carbonyl and Nitrosative Stress. In Advances in Microbial Physiology (1-22). https://doi.org/10.1016/b978-0-12-381043-4.00001-5
Journal Article
- Hong, Y., Mackenzie, E. S., Firth, S. J., Bolton, J. R. F., Stewart, L. J., Waldron, K. J., & Djoko, K. Y. (2023). Mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in Streptococcus pyogenes. Metallomics, 15(11), Article mfad064. https://doi.org/10.1093/mtomcs/mfad064
- Djoko, K. Y. (2023). Control of nutrient metal availability during host-microbe interactions: beyond nutritional immunity. JBIC Journal of Biological Inorganic Chemistry, 28(5), 451-456. https://doi.org/10.1007/s00775-023-02007-z
- Stewart, L. J., Hong, Y., Holmes, I. R., Firth, S. J., Ahmed, Y., Quinn, J., Santos, Y., Cobb, S. L., Jakubovics, N. S., & Djoko, K. Y. (2023). Salivary Antimicrobial Peptide Histatin-5 Does Not Display Zn(II)-Dependent or -Independent Activity against Streptococci. ACS Infectious Diseases, 9(3), 631-642. https://doi.org/10.1021/acsinfecdis.2c00578
- Donaghy, C., Javellana, J. G., Hong, Y.-J., Djoko, K., & Angeles-Boza, A. M. (2023). The Synergy between Zinc and Antimicrobial Peptides: An Insight into Unique Bioinorganic Interactions. Molecules, 28(5), Article 2156. https://doi.org/10.3390/molecules28052156
- Paloyan, A., Sargsyan, A., Karapetyan, M. D., Hambardzumyan, A., Kocharov, S., Panosyan, H., Dyukova, K., Kinosyan, M., Krueger, A., Piergentili, C., Stanley, W. A., Djoko, K. Y., Baslé, A., Marles‐Wright, J., & Antranikian, G. (2023). Structural and biochemical characterisation of the N‐carbamoyl‐β‐alanine amidohydrolase from Rhizobium radiobacterMDC 8606. The FEBS Journal, https://doi.org/10.1111/febs.16943
- O’Hern, C. I., & Djoko, K. Y. (2022). Copper Cytotoxicity: Cellular Casualties of Noncognate Coordination Chemistry. mBio, 13(3), e00434-22. https://doi.org/10.1128/mbio.00434-22
- Brouwer, S., Jespersen, M. G., Ong, C.-L. Y., De Oliveira, D. M., Keller, B., Cork, A. J., Djoko, K. Y., Davies, M. R., & Walker, M. J. (2022). Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion. mBio, 13(3), https://doi.org/10.1128/mbio.00676-22
- Djoko, K., & Cavet, J. (2022). Perspectives on Metals in Microbiology. Microbiology, 168(7), https://doi.org/10.1099/mic.0.001215
- Petit, G. A., Hong, Y., Djoko, K. Y., Whitten, A. E., Furlong, E. J., McCoy, A. J., Gulbis, J. M., Totsika, M., Martin, J. L., & Halili, M. A. (2022). The suppressor of copper sensitivity protein C from Caulobacter crescentus is a trimeric disulfide isomerase that binds copper(I) with subpicomolar affinity. Acta Crystallographica Section D: Structural Biology, 78(3), https://doi.org/10.1107/s2059798322000729
- Stewart, L. J., Ong, C.-L. Y., Zhang, M. M., Brouwer, S., McIntyre, L., Davies, M. R., Walker, M. J., McEwan, A. G., Waldron, K. J., & Djoko, K. Y. (2020). Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes. mBio, 11(6), e02804-20. https://doi.org/10.1128/mbio.02804-20
- Stewart, L. J., Thaqi, D., Kobe, B., McEwan, A. G., Waldron, K. J., & Djoko, K. Y. (2019). Handling of nutrient copper in the bacterial envelope. Metallomics, 11(1), 50-63. https://doi.org/10.1039/c8mt00218e
- Djoko, K. Y., Achard, M. E., Phan, M.-D., Lo, A. W., Miraula, M., Prombhul, S., Hancock, S. J., Peters, K. M., Sidjabat, H., Harris, P. N., Mitić, N., Walsh, T. R., Anderson, G. J., Shafer, W. M., Paterson, D. L., Schenk, G., McEwan, A. G., & Schembri, M. A. (2018). Copper ions and coordination complexes as novel carbapenem adjuvants. Antimicrobial Agents and Chemotherapy, 62(2), e02280-17. https://doi.org/10.1128/aac.02280-17
- Marsh, J. W., Djoko, K. Y., McEwan, A. G., & Huston, W. M. (2017). Copper(II)-bis(thiosemicarbazonato) complexes as anti-chlamydial agents. Pathogens and Disease, 75(7), Article ftx084. https://doi.org/10.1093/femspd/ftx084
- Djoko, K. Y., Phan, M.-D., Peters, K. M., Walker, M. J., Schembri, M. A., & McEwan, A. G. (2017). Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli. Proceedings of the National Academy of Sciences, 114(26), 6818-6823. https://doi.org/10.1073/pnas.1620232114
- Turner, A. G., Ong, C.-L. Y., Djoko, K. Y., West, N. P., Davies, M. R., McEwan, A. G., & Walker, M. J. (2017). The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes. Infection and Immunity, 85(6), Article e00140-17. https://doi.org/10.1128/iai.00140-17
- Couñago, R. M., Chen, N. H., Chang, C.-W., Djoko, K. Y., McEwan, A. G., & Kobe, B. (2016). Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region. Nucleic Acids Research, 44(14), 6981-6993. https://doi.org/10.1093/nar/gkw543
- Chen, N. H., Djoko, K. Y., Veyrier, F. J., & McEwan, A. G. (2016). Formaldehyde Stress Responses in Bacterial Pathogens. Frontiers in Microbiology, 7, Article 257. https://doi.org/10.3389/fmicb.2016.00257
- Djoko, K. Y., Goytia, M. M., Donnelly, P. S., Schembri, M. A., Shafer, W. M., & McEwan, A. G. (2015). Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics. Antimicrobial Agents and Chemotherapy, 59(10), 6444-6453. https://doi.org/10.1128/aac.01289-15
- Jen, F.-. C., Djoko, K., Bent, S., Day, C., McEwan, A., & Jennings, M. (2015). A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria. FASEB Journal, 29(9), 3828-3838. https://doi.org/10.1096/fj.15-270751
- Djoko, K. Y., Ong, C.-L. Y., Walker, M. J., & McEwan, A. G. (2015). The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens. Journal of Biological Chemistry, 290(31), 18954-18961. https://doi.org/10.1074/jbc.r115.647099
- Djoko, K. Y., Donnelly, P. S., & McEwan, A. G. (2014). Inhibition of respiratory Complex I by copper(ii)-bis(thiosemicarbazonato) complexes. Metallomics, 6(12), 2250-2259. https://doi.org/10.1039/c4mt00226a
- Atack, J. M., Ibranovic, I., Ong, C.-L. Y., Djoko, K. Y., Chen, N. H., vanden Hoven, R., Jennings, M. P., Edwards, J. L., & McEwan, A. G. (2014). A Role for Lactate Dehydrogenases in the Survival of Neisseria gonorrhoeae in Human Polymorphonuclear Leukocytes and Cervical Epithelial Cells. The Journal of Infectious Diseases, 210(8), 1311-1318. https://doi.org/10.1093/infdis/jiu230
- Djoko, K. Y., Paterson, B. M., Donnelly, P. S., & McEwan, A. G. (2014). Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action. Metallomics, 6(4), 854-863. https://doi.org/10.1039/c3mt00348e
- Djoko, K. Y., & McEwan, A. G. (2013). Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis. ACS Chemical Biology, 8(10), 2217-2223. https://doi.org/10.1021/cb4002443
- Atack, J. M., Srikhanta, Y. N., Djoko, K. Y., Welch, J. P., Hasri, N. H. M., Steichen, C. T., Vanden Hoven, R. N., Grimmond, S. M., Othman, D. S. M. P., Kappler, U., Apicella, M. A., Jennings, M. P., Edwards, J. L., & McEwan, A. G. (2013). Characterization of an ntrX Mutant of Neisseria gonorrhoeae Reveals a Response Regulator That Controls Expression of Respiratory Enzymes in Oxidase-Positive Proteobacteria. Journal of Bacteriology, 195(11), 2632-2641. https://doi.org/10.1128/jb.02062-12
- Chen, N. H., Couñago, R. M., Djoko, K. Y., Jennings, M. P., Apicella, M. A., Kobe, B., & McEwan, A. G. (2013). A Glutathione-Dependent Detoxification System Is Required for Formaldehyde Resistance and Optimal Survival ofNeisseria meningitidisin Biofilms. Antioxidants and Redox Signaling, 18(7), 743-755. https://doi.org/10.1089/ars.2012.4749
- Djoko, K., Franiek, J., Edwards, J., Falsetta, M., Kidd, S., Potter, A., Chen, N., Apicella, M., Jennings, M., & McEwan, A. (2012). Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress. Infection and Immunity, 80(3), 1065-1071. https://doi.org/10.1128/iai.06163-11
- Kidd, S. P., Djoko, K. Y., Ng, J., Argente, M. P., Jennings, M. P., & McEwan, A. G. (2011). A novel nickel responsive MerR-like regulator, NimR, from Haemophilus influenzae. Metallomics, 3(10), 1009-1018. https://doi.org/10.1039/c1mt00127b
- Djoko, K. Y., Chong, L. X., Wedd, A. G., & Xiao, Z. (2010). Reaction Mechanisms of the Multicopper Oxidase CueO fromEscherichia coliSupport Its Functional Role as a Cuprous Oxidase. Journal of the American Chemical Society, 132(6), 2005-2015. https://doi.org/10.1021/ja9091903
- Djoko, K. Y., Xiao, Z., & Wedd, A. G. (2008). Copper Resistance inE. coli: The Multicopper Oxidase PcoA Catalyzes Oxidation of Copper(I) in CuICuII‐PcoC. ChemBioChem, 9(10), 1579-1582. https://doi.org/10.1002/cbic.200800100
- Drew, S. C., Djoko, K. Y., Zhang, L., Koay, M., Boas, J. F., Pilbrow, J. R., Xiao, Z., Barnham, K. J., & Wedd, A. G. (2008). Electron paramagnetic resonance characterization of the copper-resistance protein PcoC from Escherichia coli. JBIC Journal of Biological Inorganic Chemistry, 13(6), 899-907. https://doi.org/10.1007/s00775-008-0377-4
- Djoko, K. Y., Xiao, Z., Huffman, D. L., & Wedd, A. G. (2007). Conserved Mechanism of Copper Binding and Transfer. A Comparison of the Copper-Resistance Proteins PcoC fromEscherichia coliand CopC fromPseudomonas syringae. Inorganic Chemistry, 46(11), 4560-4568. https://doi.org/10.1021/ic070107o
- Helfrich, M. R., Mangeney-Slavin, L. K., Long, M. S., Djoko, K. Y., & Keating, C. D. (2002). Aqueous Phase Separation in Giant Vesicles. Journal of the American Chemical Society, 124(45), 13374-13375. https://doi.org/10.1021/ja028157%2B