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Otago Medical School staff profiles

Dr Kiel Hards

PositionPostdoctoral Fellow
DepartmentDepartment of Microbiology and Immunology

Research

I am interested in the development, application and understanding of new therapeutics for both human and animal infections. I use a biochemistry guided approach, focusing on the energy generating processes of bacteria, to understand both bacterial physiology and antibiotic mode of action.

Research Questions:
- How do antibiotics cause bacterial cell death?
- Why do opportunistic pathogens need incomplete energy generating pathways?
- How do bacteria generate energy during persistence?

Publications

Santoso, K. T., Cheung, C.-Y., Hards, K., Cook, G. M., Stocker, B. L., & Timmer, M. S. M. (2019). Synthesis and investigation of phthalazinones as antitubercular agents. Chemistry: An Asian Journal. Advance online publication. doi: 10.1002/asia.201801805

Hards, K., Molano Rodriguez, S., Cairns, C., & Cook, G. M. (2019). Alternate quinone coupling in a new class of succinate dehydrogenase may potentiate mycobacterial respiratory control. FEBS Letters, 593(5), 475-486. doi: 10.1002/1873-3468.13330

Lu, X., Williams, Z., Hards, K., Tang, J., Cheung, C.-Y., Aung, H. L., … Cook, G. M. (2019). Pyrazolo[1,5-a]pyridine inhibitor of the respiratory cytochrome bcc complex for the treatment of drug-resistant tuberculosis. ACS Infectious Diseases, 5(2), 239-249. doi: 10.1021/acsinfecdis.8b00225

Harold, L. K., Antoney, J., Ahmed, F. H., Hards, K., Carr, P., Rapson, T., … Cook, G. M. (2018). FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress. Journal of Biological Chemistry. Advance online publication. doi: 10.1074/jbc.RA118.006237

Hards, K., McMillan, D. G. G., Schurig-Briccio, L. A., Gennis, R. B., Lill, H., Bald, D., & Cook, G. M. (2018). Ionophoric effects of the antitubercular drug bedaquiline. PNAS. Advance online publication. doi: 10.1073/pnas.1803723115

Chapter in Book - Research

Cook, G. M., Greening, C., Hards, K., & Berney, M. (2014). Energetics of pathogenic bacteria and opportunities for drug development. In Advances in microbial physiology. Elsevier. doi: 10.1016/bs.ampbs.2014.08.001

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Journal - Research Article

Santoso, K. T., Cheung, C.-Y., Hards, K., Cook, G. M., Stocker, B. L., & Timmer, M. S. M. (2019). Synthesis and investigation of phthalazinones as antitubercular agents. Chemistry: An Asian Journal. Advance online publication. doi: 10.1002/asia.201801805

Lu, X., Williams, Z., Hards, K., Tang, J., Cheung, C.-Y., Aung, H. L., … Cook, G. M. (2019). Pyrazolo[1,5-a]pyridine inhibitor of the respiratory cytochrome bcc complex for the treatment of drug-resistant tuberculosis. ACS Infectious Diseases, 5(2), 239-249. doi: 10.1021/acsinfecdis.8b00225

Hards, K., Molano Rodriguez, S., Cairns, C., & Cook, G. M. (2019). Alternate quinone coupling in a new class of succinate dehydrogenase may potentiate mycobacterial respiratory control. FEBS Letters, 593(5), 475-486. doi: 10.1002/1873-3468.13330

Harold, L. K., Antoney, J., Ahmed, F. H., Hards, K., Carr, P., Rapson, T., … Cook, G. M. (2018). FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress. Journal of Biological Chemistry. Advance online publication. doi: 10.1074/jbc.RA118.006237

Hards, K., McMillan, D. G. G., Schurig-Briccio, L. A., Gennis, R. B., Lill, H., Bald, D., & Cook, G. M. (2018). Ionophoric effects of the antitubercular drug bedaquiline. PNAS. Advance online publication. doi: 10.1073/pnas.1803723115

Cook, G. M., Hards, K., Dunn, E., Heikal, A., Nakatani, Y., Greening, C., … Berney, M. (2017). Oxidative phosphorylation as a target space for tuberculosis: Success, caution, and future directions. Microbiology Spectrum, 5(3), TBTB2-0014-2016. doi: 10.1128/microbiolspec.TBTB2-0014-2016

Kalia, N. P., Hasenoehrl, E. J., Ab Rahman, N. B., Koh, V. H., Ang, M. L. T., Sajorda, D. R., Hards, K., … Cook, G. M., … Pethe, K. (2017). Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection. PNAS, 114(28), 7426-7431. doi: 10.1073/pnas.1706139114

Carere, C. R., Hards, K., Houghton, K. M., Power, J. F., McDonald, B., Collet, C., … Cook, G. M., … Stott, M. B. (2017). Mixotrophy drives niche expansion of verrucomicrobial methanotrophs. ISME Journal, 11, 2599-2610. doi: 10.1038/ismej.2017.112

Medini, K., Harris, P. W. R., Menorca, A., Hards, K., Cook, G. M., & Brimble, M. A. (2016). Synthesis and activity of a diselenide bond mimetic of the antimicrobial protein caenopore-5. Chemical Science, 7(3), 2005-2010. doi: 10.1039/c5sc04187b

Heikal, A., Hards, K., Cheung, C.-Y., Menorca, A., Timmer, M. S. M., Stocker, B. L., & Cook, G. M. (2016). Activation of type II NADH dehydrogenase by quinolinequinones mediates antitubercular cell death. Journal of Antimicrobial Chemotherapy, 71(10), 2840-2847. doi: 10.1093/jac/dkw244

Greening, C., Carere, C. R., Rushton-Green, R., Harold, L. K., Hards, K., Taylor, M. C., Morales, S. E., … Cook, G. M. (2015). Persistence of the dominant soil phylum Acidobacteria by trace gas scavenging. PNAS, 112(33), 10497-10502. doi: 10.1073/pnas.1508385112

Medini, K., Harris, P. W. R., Hards, K., Dingley, A. J., Cook, G. M., & Brimble, M. A. (2015). Chemical synthesis of a pore-forming antimicrobial protein, caenopore-5, by using native chemical ligation at a Glu-Cys site. ChemBioChem, 16(2), 328-336. doi: 10.1002/cbic.201402513

Hards, K., Robson, J. R., Berney, M., Shaw, L., Bald, D., Koul, A., … Cook, G. M. (2015). Bactericidal mode of action of bedaquiline. Journal of Antimicrobial Chemotherapy, 70, 2028-2037. doi: 10.1093/jac/dkv054

Greening, C., Constant, P., Hards, K., Morales, S. E., Oakeshott, J. G., Russell, R. J., … Cook, G. M. (2015). Atmospheric hydrogen scavenging: From enzymes to ecosystems. Applied & Environmental Microbiology, 81(4), 1190-1199. doi: 10.1128/aem.03364-14

Pecsi, I., Hards, K., Ekanayaka, N., Berney, M., Hartman, T., Jacobs, Jr, W. R., & Cook, G. M. (2014). Essentiality of succinate dehydrogenase in Mycobacterium smegmatis and its role in the generation of the membrane potential under hypoxia. mBio, 5(4), e01093-14. doi: 10.1128/mBio.01093-14

Greening, C., Berney, M., Hards, K., Cook, G. M., & Conrad, R. (2014). A soil actinobacterium scavenges atmospheric H2 using two membrane-associated, oxygen-dependent [NiFe] hydrogenases. PNAS, 111(11), 4257-4261. doi: 10.1073/pnas.1320586111

McNeil, M. B., Hampton, H. G., Hards, K. J., Watson, B. N. J., Cook, G. M., & Fineran, P. C. (2014). The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. FEBS Letters, 588(3), 414-421. doi: 10.1016/j.febslet.2013.12.019

Berney, M., Greening, C., Hards, K., Collins, D., & Cook, G. M. (2014). Three different [NiFe] hydrogenases confer metabolic flexibility in the obligate aerobe Mycobacterium smegmatis. Environmental Microbiology, 16(1), 318-330. doi: 10.1111/1462-2920.12320

Cook, G. M., Hards, K., Vilchèze, C., Hartman, T., & Berney, M. (2014). Energetics of respiration and oxidative phosphorylation in mycobacteria. Microbiology Spectrum, 2(3), MGM2-0015-2013. doi: 10.1128/microbiolspec.MGM2-0015-2013

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Journal - Research Other

Hards, K., & Cook, G. M. (2018). Targeting bacterial energetics to produce new antimicrobials. Drug Resistance Updates, 36, 1-12. doi: 10.1016/j.drup.2017.11.001

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