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Health Sciences profile

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

Allen, W. J., Corey, R. A., Watkins, D. W., Oliveira, A. S. F., Hards, K., Cook, G. M., & Collinson, I. (2022). Rate-limiting transport of positively charged arginine residues through the Sec-machinery is integral to the mechanism of protein secretion. eLIFE, e77586. Advance online publication. doi: 10.7554/eLife.77586

Harold, L. K., Jinich, A., Hards, K., Cordeiro, A., Keighley, L. M., Cross, A., McNeil, M. B., … Cook, G. M. (2022). Deciphering functional redundancy and energetics of malate oxidation in mycobacteria. Journal of Biological Chemistry. Advance online publication. doi: 10.1016/j.jbc.2022.101859

Hards, K., Cheung, C.-Y., Waller, N., Adolph, C., Keighley, L., Tee, Z. S., Harold, L. K., Menorca, A., … Tyndall, J. D. A., McNeil, M. B., … Opel-Reading, H. K., Krause, K. L., … Berney, M., … Cook, G. M. (2022). An amiloride derivative is active against the F1Fo-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis. Communications Biology, 5, 166. doi: 10.1038/s42003-022-03110-8

Hards, K., Cook, G., & Jeuken, L. J. C. (2021). Bacterial respiration keeps amazing us in the 21st century. Biochemist. Advance online publication. doi: 10.1042/bio_2021_185

Fridianto, K. T., Li, M., Hards, K., Negatu, D. A., Cook, G. M., Dick, T., … Go, M.-L. (2021). Functionalized dioxonaphthoimidazoliums: A redox cycling chemotype with potent bactericidal activities against Mycobacterium tuberculosis. Journal of Medicinal Chemistry. Advance online publication. doi: 10.1021/acs.jmedchem.1c01383

McKinlay, J. B., Cook, G. M., & Hards, K. (2020). Microbial energy management: A product of three broad tradeoffs. In Advances in microbial physiology. (pp. 139-185). London, UK: Elsevier. doi: 10.1016/bs.ampbs.2020.09.001

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

Chapter in Book - Research

Allen, W. J., Corey, R. A., Watkins, D. W., Oliveira, A. S. F., Hards, K., Cook, G. M., & Collinson, I. (2022). Rate-limiting transport of positively charged arginine residues through the Sec-machinery is integral to the mechanism of protein secretion. eLIFE, e77586. Advance online publication. doi: 10.7554/eLife.77586

Journal - Research Article

Hards, K., Cheung, C.-Y., Waller, N., Adolph, C., Keighley, L., Tee, Z. S., Harold, L. K., Menorca, A., … Tyndall, J. D. A., McNeil, M. B., … Opel-Reading, H. K., Krause, K. L., … Berney, M., … Cook, G. M. (2022). An amiloride derivative is active against the F1Fo-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis. Communications Biology, 5, 166. doi: 10.1038/s42003-022-03110-8

Journal - Research Article

Harold, L. K., Jinich, A., Hards, K., Cordeiro, A., Keighley, L. M., Cross, A., McNeil, M. B., … Cook, G. M. (2022). Deciphering functional redundancy and energetics of malate oxidation in mycobacteria. Journal of Biological Chemistry. Advance online publication. doi: 10.1016/j.jbc.2022.101859

Journal - Research Article

Carere, C. R., Hards, K., Wigley, K., Carman, L., Houghton, K. M., Cook, G. M., & Stott, M. B. (2021). Growth on formic acid is dependent on intracellular pH homeostasis for the thermoacidophilic methanotroph Methylacidiphilum sp. RTK17.1. Frontiers in Microbiology, 12, 651744. doi: 10.3389/fmicb.2021.651744

Journal - Research Article

Fridianto, K. T., Li, M., Hards, K., Negatu, D. A., Cook, G. M., Dick, T., … Go, M.-L. (2021). Functionalized dioxonaphthoimidazoliums: A redox cycling chemotype with potent bactericidal activities against Mycobacterium tuberculosis. Journal of Medicinal Chemistry. Advance online publication. doi: 10.1021/acs.jmedchem.1c01383

Journal - Research Article

Safarian, S., Opel-Reading, H. K., Wu, D., Mehdipour, A. R., Hards, K., Harold, L. K., … Stewart, I., … Cook, G. M., Krause, K. L., & Michel, H. (2021). The cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB. Nature Communications, 12(1), 5236. doi: 10.1038/s41467-021-25537-z

Journal - Research Article

Harbison-Price, N., Ferguson, S. A., Heikal, A., Taiaroa, G., Hards, K., Nakatani, Y., … Cook, G. M. (2020). Multiple bactericidal mechanisms of the zinc ionophore PBT2. mSphere, 5(2), e00157-20. doi: 10.1128/mSphere.00157-20

Journal - Research Article

Lee, B. M., Harold, L. K., Almeida, D. V., Afrait-Jurnou, L., Aung, H. L., Forde, B. M., Hards, K., … Cook, G. M., & Jackson, C. J. (2020). Predicting nitroimidazole antibiotic resistance mutations in Mycobacterium tuberculosis with protein engineering. PLoS Pathogens, 16(2), e1008287. doi: 10.1371/journal.ppat.1008287

Journal - Research Article

Lee, B. S., Hards, K., Engelhart, C. A., Hasenoehrl, E. J., Kalia, N. P., Mackenzie, J. S., … Cook, G. M., … Pethe, K. (2020). Dual inhibition of the terminal oxidases eradicates antibiotic-tolerant Mycobacterium tuberculosis. EMBO Molecular Medicine, e13207. Advance online publication. doi: 10.15252/emmm.202013207

Journal - Research Article

Nizi, M. G., Desantis, J., Nakatani, Y., Massari, S., Mazzarella, M. A., Shetye, G., … Hards, K., … Cook, G. M., … Tabarrini, O. (2020). Antitubercular polyhalogenated phenothiazines and phenoselenazine with reduced binding to CNS receptors. European Journal of Medicinal Chemistry, 201, 112420. doi: 10.1016/j.ejmech.2020.112420

Journal - Research Article

Cordero, P. R. F., Grinter, R., Hards, K., Cryle, M. J., Warr, C. G., Cook, G. M., & Greening, C. (2019). Two uptake hydrogenases differentially interact with the aerobic respiratory chain during mycobacterial growth and persistence. Journal of Biological Chemistry, 294(50), 18980-18991. doi: 10.1074/jbc.RA119.011076

Journal - Research Article

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

Journal - Research Article

Harold, L. K., Antoney, J., Ahmed, F. H., Hards, K., Carr, P., Rapson, T., … Cook, G. M. (2019). FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress. Journal of Biological Chemistry, 294(8), 2903-2912. doi: 10.1074/jbc.RA118.006237

Journal - Research Article

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

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, 14, 1278-1285. doi: 10.1002/asia.201801805

Journal - Research Article

Saw, W.-G., Wu, M.-L., Ragunathan, P., Biuković, G., Lau, A.-M., Shin, J., … Hards, K., … Cook, G. M., … Grüber, G. (2019). Disrupting coupling within mycobacterial F-ATP synthases subunit ε causes dysregulated energy production and cell wall biosynthesis. Scientific Reports, 9, 16759. doi: 10.1038/s41598-019-53107-3

Journal - Research Article

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, 115(28), 7326-7331. doi: 10.1073/pnas.1803723115

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

Hards, K., Cook, G., & Jeuken, L. J. C. (2021). Bacterial respiration keeps amazing us in the 21st century. Biochemist. Advance online publication. doi: 10.1042/bio_2021_185

Journal - Research Other

Hards, K., Adolph, C., Harold, L. K., McNeil, M. B., Cheung, C.-Y., Jinich, A., … Cook, G. M. (2020). Two for the price of one: Attacking the energetic-metabolic hub of mycobacteria to produce new chemotherapeutic agents. Progress in Biophysics & Molecular Biology, 152, 35-44. doi: 10.1016/j.pbiomolbio.2019.11.003

Journal - Research Other

Jeuken, L. J. C., Hards, K., & Nakatani, Y. (2020). Extracellular electron transfer: Respiratory or nutrient homeostasis? Journal of Bacteriology, 202(7), e0002920. doi: 10.1128/jb.00029-20

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

Journal - Research Other

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