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 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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