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. Uncovering the hidden antibiotic potential of
Cannabis. BioRxiv 833392; doi:http://dx.doi.org/10.1101/833392
We will adhere to the Universal Principled (UP) Review guidelines
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Principled Review: A Community-Driven Method to Improve Peer Review.Krummel M, Blish C, Kuhns M, Cadwell K, Oberst A, Goldrath A, Ansel KM,
Chi H, O’Connell R, Wherry EJ, Pepper M; Future Immunology Consortium.Cell . 2019 Dec 12;179(7):1441-1445. doi:
10.1016/j.cell .2019.11.029.
SUMMARY : In this study, Farha, et al . investigate
candidate antibiotics from Cannabis sativa . Eighteen molecules
from C. sativa were screened for antibiotic activity against
methicillin-resistant Staphylococcus aureus (MRSA). Of these,
seven compounds were identified as potential antibiotics (min.
inhibitory concentration [MIC] < 2 µg/mL). The cannabinoid
cannabigerol (CBG) displayed the highest efficacy against biofilms,
free-living MRSA, and MRSA persister cells. The authors used a variety
of approaches to investigate CBG mechanism of action, including attempts
to isolate drug-resistant bacteria via spontaneous resistance, serial
passaging, knockdown libraries and transposon mutant libraries. They
were unable to identify a single CBG-resistant bacterium. However, they
determined that CBG affects the membrane stability of Gram-positive
bacteria. Finally, they found that CBG alone had no effect on
Gram-negative bacteria, but displayed antibiotic activity when combined
with polymyxin B. Overall, this paper shows that there are multiple
metabolites produced by Cannabis sativa that have antibacterial
properties and that CBG can kill bacterial cells and disrupt bacterial
biofilms by interfering with stability of the inner membrane.