Projects per year
Personal profile
Research interests
My work broadly focuses on β-lactam antibiotic action and resistance in Gram-negative pathogens.
β-Lactams, the most prescribed antibiotic class worldwide, kill bacteria by binding and inhibiting Penicillin Binding Proteins (PBPs). β-Lactam resistance can be conferred by β-lactamases (BLAs), enzymes evolutionarily related to PBPs that inactivate the antibiotics, threatening their continued clinical efficacy.
I use interdisciplinary approaches in microbiology, biochemistry, structural biology, and biomolecular simulation to advance the understanding of PBP/BLA mechanisms and inhibition.
External positions
Honorary Research Fellow, University of Bristol
1 Sept 2023 → 31 Aug 2025
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Projects
- 1 Active
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Understanding ß-lactam antibiotic action and resistance in Klebsiella pneumoniae through penicillin binding protein characterisation.
Tooke, C. (PI)
1/07/25 → 30/06/30
Project: Research council
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Dynamic Behavior and Substrate Interactions of the Polymyxin Resistance Determinant MCR-1 Investigated by Molecular Dynamics Simulations in the Membrane Environment
Lythell, E., Badley, J., Suardíaz, R., Gurr, C. R., Tooke, C. L., Hinchliffe, P., Oliveira, A. S. F., Van der Kamp, M. W., Spencer, J. & Mulholland, A. J., 11 Aug 2025, In: Journal of Chemical Information and Modeling. 65, 15, p. 8322-8334 13 p.Research output: Contribution to journal › Article › peer-review
Open Access -
Electrostatic interactions influence diazabicyclooctane inhibitor potency against OXA-48-like β-lactamases
Hoff, J. F., Goudar, K. E., Calvopiña, K., Beer, M., Hinchliffe, P., Shaw, J. M., Tooke, C. L., Takebayashi, Y., Cadzow, A. F., Harmer, N. J., Mulholland, A. J., Schofield, C. J. & Spencer, J., 8 Aug 2025, (E-pub ahead of print) In: RSC Medicinal Chemistry.Research output: Contribution to journal › Article › peer-review
Open Access -
Harvesting and amplifying gene cassettes confers cross-resistance to critically important antibiotics
Dulyayangkul, P., Beavis, T., Lee, W. W. Y., Ardagh, R., Edwards, F., Hamilton, F., Head, I., Heesom, K. J., Mounsey, O., Murarik, M., Pinweha, P., Reding, C., Satapoomin, N., Shaw, J. M., Takebayashi, Y., Tooke, C. L., Spencer, J., Williams, P. B. & Avison, M. B., 6 Jun 2024, In: PLoS Pathogens. 20, 6 , e1012235.Research output: Contribution to journal › Article › peer-review
Open Access3 Citations (SciVal) -
Tautomer-Specific Deacylation and Ω-Loop Flexibility Explain the Carbapenem-Hydrolyzing Broad-Spectrum Activity of the KPC-2 β-Lactamase
Tooke, C., Hinchliffe, P., Beer, M., Zinovjev, K., Colenso, C. K., Schofield, C., Mulholland, A. & Spencer, J., 5 Apr 2023, In: Journal of the American Chemical Society.Research output: Contribution to journal › Article › peer-review
Open Access16 Citations (SciVal) -
Penicillanic Acid Sulfones Inactivate the Extended-Spectrum β-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of β-Lactamase Inhibition
Hinchliffe, P., Tooke, C., Bethel, C. R., Wang, B., Arthur, C., Heesom, K. J., Shapiro, S., Schlatzer, D. M., Papp-Wallace, K. M., Bonomo, R. A. & Spencer, J., 25 May 2022, In: mBio. 13, 3, 16 p., e01793-21.Research output: Contribution to journal › Article › peer-review
Open Access9 Citations (SciVal)