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Uncovering the hidden antibiotic potential of Cannabis

Maya A. Farha, View ORCID ProfileOmar M. El-Halfawy, Robert T. Gale, Craig R. MacNair, Lindsey A. Carfrae, Xiong Zhang, Nicholas G. Jentsch, Jakob Magolan, Eric D. Brown
doi: https://doi.org/10.1101/833392
Maya A. Farha
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Omar M. El-Halfawy
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
3Microbiology and Immunology Department, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
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  • ORCID record for Omar M. El-Halfawy
Robert T. Gale
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Craig R. MacNair
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Lindsey A. Carfrae
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Xiong Zhang
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Nicholas G. Jentsch
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Jakob Magolan
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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Eric D. Brown
1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
2Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada
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  • For correspondence: ebrown@mcmaster.ca
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Abstract

The spread of antimicrobial resistance continues to be a priority health concern worldwide, necessitating exploration of alternative therapies. Cannabis sativa has long been known to contain antibacterial cannabinoids, but their potential to address antibiotic resistance has only been superficially investigated. Here, we show that cannabinoids exhibit antibacterial activity against MRSA, inhibit its ability to form biofilms and eradicate stationary phase cells persistent to antibiotics. We show that the mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA. We also show that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where cannabigerol acts on the inner membrane. Finally, we demonstrate that cannabinoids work in combination with polymyxin B against multi-drug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.

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Posted November 08, 2019.
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Uncovering the hidden antibiotic potential of Cannabis
Maya A. Farha, Omar M. El-Halfawy, Robert T. Gale, Craig R. MacNair, Lindsey A. Carfrae, Xiong Zhang, Nicholas G. Jentsch, Jakob Magolan, Eric D. Brown
bioRxiv 833392; doi: https://doi.org/10.1101/833392
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Uncovering the hidden antibiotic potential of Cannabis
Maya A. Farha, Omar M. El-Halfawy, Robert T. Gale, Craig R. MacNair, Lindsey A. Carfrae, Xiong Zhang, Nicholas G. Jentsch, Jakob Magolan, Eric D. Brown
bioRxiv 833392; doi: https://doi.org/10.1101/833392

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