Journal article
Chemical synergy between ionophore PBT2 and zinc reverses antibiotic resistance
L Bohlmann, DMP De Oliveira, IM El-Deeb, EB Brazel, N Harbison-Price, CLY Ong, T Rivera-Hernandez, SA Ferguson, AJ Cork, MD Phan, AT Soderholm, MR Davies, GR Nimmo, G Dougan, MA Schembri, GM Cook, AG McEwan, M von Itzstein, CA McDevitt, MJ Walker
Mbio | AMER SOC MICROBIOLOGY | Published : 2018
Abstract
The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer’s and Huntington’s disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptoco..
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Funding Acknowledgements
M.A.S. and M.J.W. are recipients of National Health and Medical Research Council of Australia Fellowships. C.-L.Y.O. is a Garnett Passe & Rodney Williams Memorial Foundation Research Fellow. C.A.M. is a recipient of an Australian Research Council Future Fellowship. This work was supported by the National Health and Medical Research Council of Australia.