Dr Kiel Hards

2024

Journal - Research Article

Adolph, C., Hards, K., Williams, Z. C., Cheung, C.-Y., Keighley, L. M., Jowsey, W. J., Kyte, M., … McNeil, M. B., & Cook, G. M. (2024). Identification of chemical scaffolds that inhibit the Mycobacterium tuberculosis respiratory complex succinate dehydrogenase. ACS Infectious Diseases, 10, 3496-3515. doi: 10.1021/acsinfecdis.3c00655

Adolph, C., Cheung, C.-Y., McNeil, M. B., Jowsey, W. J., Williams, Z. C., Hards, K., Harold, L. K., … Tyndall, J. D. A., … Cook, G. M. (2024). A dual-targeting succinate dehydrogenase and F₁F_o-ATP synthase inhibitor rapidly sterilizes replicating and non-replicating Mycobacterium tuberculosis. Cell Chemical Biology, 31(4), 683-698. doi: 10.1016/j.chembiol.2023.12.002

2023

Journal - Research Article

Kalia, N. P., Singh, S., Hards, K., Cheung, C.-Y., Sviriaeva, E., Banaei-Esfahani, A., … Cook, G. M., & Pethe, K. (2023). M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments. Cell Reports, 42, 112444. doi: 10.1016/j.celrep.2023.112444

2022

Journal - Research Article

Harris, P. W. R., Siow, A., Yang, S.-H., Wadsworth, A. D., Tan, L., Hermant, Y., … Ferguson, S. A., Mros, S., Hards, K., Cook, G. M., … Brimble, M. A. (2022). Synthesis, antibacterial activity, and nephrotoxicity of polymyxin B analogues modified at Leu-7, D-Phe-6, and the N-terminus enabled by S-lipidation. ACS Infectious Diseases, 8, 2413-2429. doi: 10.1021/acsinfecdis.1c00347

Fridianto, K. T., Gunawan, G. A., Hards, K., Sarathy, J. P., Cook, G. M., Dick, T., … Lam, Y. (2022). Alkyltriphenylphosphonium turns naphthoquinoneimidazoles into potent membrane depolarizers against mycobacteria. RSC Medicinal Chemistry, 13, 1605-1613. doi: 10.1039/d2md00251e

Lawer, A., Tyler, C., Hards, K., Keighley, L. M., Cheung, C.-Y., Kierek, F., Su, S., … McInnes, T., Tyndall, J. D. A., Krause, K. L., Cook, G. M., & Gamble, A. B. (2022). Synthesis and biological evaluation of aurachin D analogues as inhibitors of Mycobacterium tuberculosis cytochrome bd oxidase. ACS Medicinal Chemistry Letters, 13, 1663-1669. doi: 10.1021/acsmedchemlett.2c00401

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, 11, e77586. 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, 298(5), 101859. 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 F₁F_o-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis. Communications Biology, 5, 166. doi: 10.1038/s42003-022-03110-8

Conference Contribution - Verbal presentation and other Conference outputs

Safarian, S., Opel-Reading, H. K., Hards, K., Harold, L. K., Cook, G. M., Krause, K. L., & Michel, H. (2022, August). BD oxidase is a game-changing drug discovery target for tuberculosis. Verbal presentation at the Webster Centre for Infectious Diseases Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

2021

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, 64, 15991-16007. doi: 10.1021/acs.jmedchem.1c01383

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

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 Other

Hards, K., Cook, G., & Jeuken, L. J. C. (2021). Bacterial respiration keeps amazing us in the 21st century. Biochemist, 43(6), 22-26. doi: 10.1042/bio_2021_185

Conference Contribution - Published proceedings: Abstract

Safarian, S., Opel-Reading, H. K., Hards, K., Harold, L. K., Cook, G. M., Krause, K. L., & Michel, H. (2021). Structure of BD oxidase from Mycobacteria as a game-changing target in TB drug design. Proceedings of the 16th Congress of the Federation of Asian & Oceanic Biochemists & Molecular Biologists (FAOBMB). (pp. 303). Retrieved from https://www.faobmb2021.org

2020

Chapter in Book - Research

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

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, 13, e13207. doi: 10.15252/emmm.202013207

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

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

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 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

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

2019

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

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

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

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. (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

Conference Contribution - Poster Presentation (not in published proceedings)

Hards, K. (2019, August-September). Differential and oxygen-independent roles of the two terminal oxidases in mycobacteria. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Conference Contribution - Verbal presentation and other Conference outputs

Greening, C., Grinter, R., Ahmed, F. H., Bashiri, G., Ney, B., Lee, B. M., Hards, K., … Cook, G. M., … Jackson, C. J. (2019, August-September). The hows and whys of cofactor F₄₂₀ biosynthesis in mycobacteria. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

McNeil, M., Adolph, C., Cheung, C.-Y., Hards, K., Jinich, A., Rhee, K., & Cook, G. M. (2019, August-September). Essentiality of succinate metabolism in Mycobacterium tuberculosis. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Cheung, J., Adolph, C., Buckley, B. J., Majed, H., Aboelela, A., Bujaroski, R., … Hards, K., McNeil, M. B., … Cook, G. M. (2019, August-September). Next generation ATP synthase inhibitors to combat drug resistant tuberculosis. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

2018

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 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

Conference Contribution - Published proceedings: Abstract

Harold, L. K., Antoney, J., Ahmed, F. H., Hards, K., Carr, P. D., Rapson, T., … Cook, G. M. (2018). Identification and characterization of a FAD chaperon required for mycobacterial survival under hypoxia. Proceedings of the New Zealand Microbiological Society (NZMS) New Zealand Society for Biochemistry and Molecular Biology (NZSBMB) Joint Annual Conference: Microbes & Molecules. (pp. 111). Retrieved from https://www.nzmsconference.org.nz

Adolph, C., Cheung, J., Buckley, B. J., Aboelela, A., Hards, K., McNeil, M., … Cook, G. M. (2018). Identification of novel antimicrobials targeting succinate dehydrogenase in Mycobacterium tuberculosis. Proceedings of the New Zealand Microbiological Society (NZMS) New Zealand Society for Biochemistry and Molecular Biology (NZSBMB) Joint Annual Conference: Microbes & Molecules. (pp. 54-55). Retrieved from https://www.nzmsconference.org.nz

Harbison-Price, N., Ferguson, S. A., Heikal, A., Taiaroa, G., Hards, K., Mros, S., … Cook, G. M. (2018). Investigating the antimicrobial action of a zinc ionophore in the mastitis-causing pathogen Streptococcus uberis. Proceedings of the New Zealand Microbiological Society (NZMS) New Zealand Society for Biochemistry and Molecular Biology (NZSBMB) Joint Annual Conference: Microbes & Molecules. (pp. 39). Retrieved from https://www.nzmsconference.org.nz

Williams, Z., Hards, K., Li, X., Ding, K., & Cook, G. M. (2018). Next generation inhibitors to combat drug resistant tuberculosis infections. Proceedings of the New Zealand Microbiological Society (NZMS) New Zealand Society for Biochemistry and Molecular Biology (NZSBMB) Joint Annual Conference: Microbes & Molecules. (pp. 35). Retrieved from https://www.nzmsconference.org.nz

2017

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

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

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

Conference Contribution - Published proceedings: Abstract

Carere, C. R., Hards, K., Houghton, K. M., Power, J. F., McDonald, B., Collet, C., … Cook, G. M., Greening, C., & Stott, M. B. (2017). Mixotrophy drives niche expansion of thermoacidopholic methanotrophs. Proceedings of the New Zealand Microbiological Society (NZMS) Annual Conference. 155. Retrieved from http://www.nzmsconference.org.nz/

Conference Contribution - Poster Presentation (not in published proceedings)

Hards, K. (2017, September). Ionophoric effects of the antitubercular drug bedaquiline. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Harold, L. K., Ahmed, F. H., Antoney, J., Hards, K., Greening, C., Jackson, C. J., & Cook, G. M. (2017, September). MSMEG_5243: A succinate dehydrogenase flavination factor. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Awarded Doctoral Degree

Hards, K. J. (2017). Fundamental and applied investigations into mycobacterial bioenergetics (PhD). University of Otago, Dunedin, New Zealand. Retrieved from http://hdl.handle.net/10523/7474

2016

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

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

Conference Contribution - Published proceedings: Abstract

Hards, K., & Cook, G. M. (2016). Compartmentalization of succinate dehydrogenase function in the diverse lifestyle conditions of an actinobacterium. Biochimica et Biophysica Acta: Bioenergetics, 1857(Suppl.), (pp. e86-e87). doi: 10.1016/j.bbabio.2016.04.210

Conference Contribution - Verbal presentation and other Conference outputs

Carere, C. R., Hards, K., Greening, C., Gapes, D., Sparling, R., Cook, G. M., & Stott, M. B. (2016, November). Hydrogen metabolism within the thermoacidophilic methane oxidising bacterium, Methylacidiphilum sp. RTK17.1. Verbal presentation at the Joint Meeting of the New Zealand Microbiological Society (NZMS) and the New Zealand Society for Biochemistry and Molecular Biology (NZSBMB), Christchurch, New Zealand.

Williams, Z. C., Hards, K., Aung, H. L., & Cook, G. M. (2016, November). Regulation of cytochrome bd in mycobacteria in response to carbon and oxygen availability. Verbal presentation at the Joint Meeting of the New Zealand Microbiological Society (NZMS) and the New Zealand Society for Biochemistry and Molecular Biology (NZSBMB), Christchurch, New Zealand.

Cook, G., & Hards, K. (2016, August-September). New TB drugs work by a common mechanism: Uncouplers of the respiratory chain. Verbal presentation at the Queenstown Molecular Biology (QMB) Meetings, Nelson, New Zealand.

2015

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

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

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

Conference Contribution - Poster Presentation (not in published proceedings)

Heikal, A., Nakatani, Y., Dunn, E. A., Hards, K., Tee, Z. S., Lott, J. S., & Cook, G. M. (2015, August-September). Building a framework for OXPHOS inhibitor discovery: The structure and mechanism of type II NADH dehydrogenase. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

Hards, K., & Cook, G. M. (2015, August-September). Novel mode of action for a new TB drug. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.

2014

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

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

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

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

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