Cannabidiol (CBD) repurposing as antibacterial: promising therapy of CBD plus polymyxin B against superbugs

Abichabki, N.; Zacharias, L. V.; Moreira, N. C.; Bellissimo-Rodrigues, F.; Moreira, F. d. L.; Benzi, J. R. d. L.; Ogasawara, T. M. C.; Ferreira, J. C.; Pereira, L. R. L.; Braga, G. U. L.; Ribeiro, C. M.; Pavan, F. R.; Zuardi, A. W.; Hallak, J. E. C.; Crippa, J. A. d. S.; Lanchote, V. L.; Canton, R.; Darini, A. L. C.; Andrade, L. N.

doi:10.1101/2021.04.12.439341

bioRxiv · 10.1101/2021.04.12.439341

Cannabidiol (CBD) repurposing as antibacterial: promising therapy of CBD plus polymyxin B against superbugs

Abichabki, N.·Zacharias, L. V.·Moreira, N. C.·Bellissimo-Rodrigues, F.·Moreira, F. d. L.·Benzi, J. R. d. L.·Ogasawara, T. M. C.·Ferreira, J. C.·Pereira, L. R. L.·Braga, G. U. L.·Ribeiro, C. M.·Pavan, F. R.·Zuardi, A. W.·Hallak, J. E. C.·Crippa, J. A. d. S.·Lanchote, V. L.·Canton, R.·Darini, A. L. C.·Andrade, L. N.

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Abstract

Abstract Multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are a major worldwide public health problem. In the last decades, resistance to last-resort antibiotics such as polymyxin B (PB) have been increasingly observed among these superbugs, compromising the effectiveness of antimicrobial therapy. The present study aimed (i) to assess the ultrapure Cannabidiol (CBD) antibacterial activity against a broad diversity of Gram-negative (GN) and Gram-positive (GP) bacteria (44 different species, 95 strains), comprising standard strains and clinical isolates, and (ii) to investigate the antibacterial activity of the combination CBD + PB against GN bacteria, including chromosomal- and plasmid-acquired PB-resistant and intrinsically PB-resistant GNB. We evaluated CBD in vitro antibacterial activity using the standard broth microdilution method, and the antibacterial activity of the combination CBD + PB was screened using the standard broth microdilution and confirmed by checkerboard assay. CBD exhibited antibacterial activity against different GP bacterial species, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, and Moraxella catarrhalis), and Mycobacterium tuberculosis. The combination CBD + PB exhibited antibacterial activity against PB-resistant GNB (e.g., Klebsiella pneumoniae) as well as additive and/or synergistic effect against LOS-expressing GND. The antibacterial activity of the combination CBD + PB against Pseudomonas aeruginosa and plasmid-mediated colistin-resistant (MCR-1) E. coli strains could be only demonstrated in the presence of phenylalanine-arginine-{beta}-naphthylamide (PA{beta}N). In conclusion, our results show promising translational potential of the combination CBD + PB against MDR and XDR GNB, including PB-resistant K. pneumoniae, highlighting its potential as a rescue treatment for life-threatening infections caused by these superbugs. One Sentence SummaryPromising combination of cannabidiol (CBD) + polymyxin B (PB) against superbugs (e.g., PB-resistant Gram-negative bacilli): Repurposing CBD

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Abichabki, N., Zacharias, L. V., Moreira, N. C., Bellissimo-Rodrigues, F., Moreira, F. d. L., Benzi, J. R. d. L., Ogasawara, T. M. C., Ferreira, J. C., Pereira, L. R. L., Braga, G. U. L., Ribeiro, C. M., Pavan, F. R., Zuardi, A. W., Hallak, J. E. C., Crippa, J. A. d. S., Lanchote, V. L., Canton, R., Darini, A. L. C., Andrade, L. N.. 2021-04-12. Cannabidiol (CBD) repurposing as antibacterial: promising therapy of CBD plus polymyxin B against superbugs. https://doi.org/10.1101/2021.04.12.439341

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