“Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic-resistant Gram-positive bacteria,” the researchers stated.
Antibiotics have saved millions of lives worldwide since the discovery of penicillin, but over time bacteria have developed mechanisms to escape the effects of antibiotics leading to multi-drug resistance adding to an increased global health threat.
“With fewer antibiotics available to treat MDR bacterial infections, the possibility of entering a pre-antibiotic era is looming ahead,” the team stated.
Around the globe alternative strategies are being explored that may be able to help address antibiotic resistance, including helper compounds which are also known as antibiotic potentiators or resistant breakers, which are non-antibiotic compounds that can act as adjuvants for antibiotics that operate synergistically through mechanisms including enzyme inhibition, efflux pump inhibition or changing membrane permeability; all of which can contribute to helping to improve antibiotic efficacy.
Overuse of antibiotics may well be one of the main causes of antibiotic resistance, the combination of an antibiotic with a helper may help to reduce the amount of antibiotics needed to achieve bacterial growth inhibition or even kill it if the antibiotic was then used alone. CBD has been observed to inhibit bacterial growth, but its use as an antibiotic adjuvant has not been investigated.
“This strategy may, therefore, decrease the likelihood of resistance development, and investigations to identify efficient helper compounds are thus important,” the investigators suggested.
“Not much is known regarding antimicrobial effects of cannabinoids and even less on the mechanism of action … the use of cannabidiol as an antibiotic adjuvant has not been studied so far.”
This study was designed to evaluate whether CBD could act as a potential helper compound to increase the effectiveness of the antibiotic bacitracin, which is mixture of cyclic peptides that interfere with the bacterial cell walls and interrupts the biosynthesis of peptidoglycan against Gram positive bacteria methicillin resistant MRSA and MRSE. The effects of combining CBD and BAC were then tested against different Gram positive bacteria, results provided initial indication that CBD could potentiate the antimicrobial effects of the antibiotic according to the team.
Additional testing with the combination against S. aureus showed that dual treatment caused morphological changes in bacterial cells that affected cell division such that the bacteria could no longer divide normally, and these effects were not seen with either treatment on its own.
“… the combination of CBD and BAC affects the cell envelope causing irregular cell division visualized by multiple septa formations and irregular cell membrane.” the authors write, and that “… CBD and BAC alone caused no morphological changes.”
Combined treatment was also observed to decrease autolysis in S. aureus, and CBD was shown to cause depolarization of the cytoplasmic membrane; gene expression analysis confirmed treatment using the combination resulted in reduced expression of key cell division and autolysis genes in the bacteria.
The combination treatment was not effective in Gram negative bacteria, a mixture of cyclic peptides that interrupt cell wall synthesis in Gram positive bacteria, and the antibiotic is most likely unable to cross the outer membrane in Gram negative bacteria, according to the researchers.
“In this study, we found that the antibacterial effects of BAC against S. aureus as well as other Gram-positive bacteria can be enhanced by cannabidiol originating from the cannabis plant,” the scientists concluded, who acknowledged that further work will be needed to understand the mechanisms of action of combined CBD and BAC treatment on Gram-positive bacteria. “Changes observed in morphology were not caused by compositional changes in the cell wall muropeptide composition. Membrane potential changes for the combination of CBD and BAC compared to either CBD or BAC treatment alone did not reveal the mechanism of action for the combination of CBD and BAC,” they wrote. “Future studies are therefore focused on the cell division and cell envelope to identify the mechanism of action.”
