PI Greg Cook is a Microbiologist with a strong research interest in bacterial physiology and energetics, antimicrobial resistance (AMR) and drug discovery and development. His group joined CIIC located at QIMR-Berghofer in 2025 and research projects in the AMR Solutions Lab are multidisciplinary, spanning human biomedical and agritech/biotech, and cover basic to translational research. Research from the AMR Solutions Lab is aimed at providing fundamental knowledge on the metabolism and energetics of bacterial pathogens like Mycobacterium tuberculosis. A major goal of his research is to translate these findings into new drug target development to combat AMR, tolerance and virulence, and provide molecular and mechanistic insight into the mode of action of antimicrobials. A key component of this work is to uncover genetic vulnerabilities in drug-resistance strains that can be exploited to develop new strategies and combination therapies.
A second major theme of the AMR Solutions Lab is aimed at preserving human, animal and plant health in the face of AMR through the discovery and implementation of compounds that are used exclusively in animals and plants to combat environmental pathogens like mastitis-causing bacteria and fungal pathogens of plants. Part of this theme includes discovering new inhibitors for management of greenhouse gas emissions in ruminant animals and soils (in collaboration with Professors Phil Pope and Gene Tyson, Centre for Microbiome Research).
Team members
- Dr Yvette Ong – postdoctoral fellow
- James Cheung – PhD Candidate
- Caitlin Cleary – PhD Candidate
Current projects in AMR solutions:
Harnessing drug efflux pump inhibition to accelerate TB therapy and combat drug resistance
See recent publications:
Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis. Xiong Z, Yang X, Wang S, Smart CJ, Sisson HM, Lin Z, Hu T, Ran Y, Xu C, Yang X, Zhao Y, Jowsey WJ, Cook GM, McNeil MB, Guddat LW, Rao Z, Zhang B. Nat Commun. 2025 May 29;16(1):4976. doi: 10.1038/s41467-025-60365-5.PMID: 40442140
Verapamil and its metabolite norverapamil inhibit the Mycobacterium tuberculosis MmpS5L5 efflux pump to increase bedaquiline activity. Fountain AJ, Waller NJE, Cheung CY, Jowsey W, Chrisp MT, Troll M, Edelstein PH, Cook GM, McNeil MB, Ramakrishnan L. Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2426827122. doi: 10.1073/pnas.2426827122.
Disrupting Bacterial Metal Ion Homeostasis to Break Antimicrobial Resistance
See recent publications:
Van Zuylen EM, Ferguson SA, Hughes A, Rennison D, Brimble MA and GM Cook. Disruption of metallostasis in the anaerobic human pathogen Fusobacterium nucleatum by the zinc ionophore PBT2. ACS Infectious Diseases 2021 Jul 14. doi: 10.1021/acsinfecdis.0c00887
De Oliveira DMP, Bohlmann L, Conroy T, Jen FE, Everest-Dass A, Hansford KA, Bolisetti R, El-Deeb IM, Forde BM, Phan MD, Lacey JA, Tan A, Rivera-Hernandez T, Brouwer S, Keller N, Kidd TJ, Cork AJ, Bauer MJ, Cook GM, Davies MR, Beatson SA, Paterson DL, McEwan AG, Li J, Schembri MA, Blaskovich MAT, Jennings MP, McDevitt CA, von Itzstein M and MJ Walker. Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis. Science Translational Medicine 12, eabb3791 (2020)
Unlocking Antimicrobial Tolerance and Virulence in Bacterial Pathogens to Overcome AMR
RfaH as an anti-virulence target. RfaH is a highly conserved transcriptional regulator of key virulence factors in gram-negative bacteria. It plays a crucial role in regulating the transcription and expression of these virulence factors, and deletion of RfaH has been shown to significantly attenuate virulence and colonisation in mice models. Despite its strong potential as a drug target, progress to utilise it as an antimicrobial target has only begun recently in limited areas. Hence, we aim to identify potential candidates that directly target RfaH via various screening methods. We hope to eventually generate a broad-spectrum anti-virulence drug or adjuvant for currently available drugs and/or antibiotics.
See recent publications:
The two-component system CroRS acts as a master regulator of cell envelope homeostasis to confer antimicrobial tolerance in the bacterial pathogen Enterococcus faecalis. Todd Rose FO, Darnell RL, Morris SM, Rose OE, Paxie O, Campbell G, Cook GM, Gebhard S. Mol Microbiol. 2023 Sep;120(3):408-424. doi: 10.1111/mmi.15128. Epub 2023 Jul 20.PMID: 37475106
Antimicrobial tolerance and its role in the development of resistance: Lessons from enterococci. Darnell RL, Paxie O, Todd Rose FO, Morris S, Krause AL, Monk IR, Smith MJB, Stinear TP, Cook GM, Gebhard S. Adv Microb Physiol. 2022;81:25-65. doi: 10.1016/bs.ampbs.2022.06.004. Epub 2022 Jul 18.PMID: 36167442
If you require more detailed information on these projects, please email: g3.cook@qut.edu.au