Cannabidiol (CBD) repurposing as antibacterial: promising therapy of 1 CBD plus polymyxin B against superbugs

Nathália Abichabki, Luísa V. Zacharias, Natália C. Moreira, Fernando Bellissimo-Rodrigues, Fernanda L. Moreira, Jhohann R. L. Benzi1, Tânia M. C. Ogasawara, Joseane C.  Ferreira, Leonardo R. L. Pereira, Gilberto Ú. L. Braga, Camila M. Ribeiro, Fernando R.  Pavan, Antonio W. Zuardi, Jaime E. C. Hallak, José A. S. Crippa, Vera L. Lanchote,  Rafael Cantón, Ana Lúcia C. Darini, Leonardo N. Andrade

bioRxiv preprint, 2021

doi : 10.1101/2021.04.12.439341

 

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 (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-β-naphthylamide (PAβN).

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.

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Canabidiolagainstsuperbugs_bioRxiv_2021