Combination of cannabidiol and bacitracin against bacterial infections

Claes Søndergaard Wassmann

Research output: ThesisPh.D. thesis

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Emergence of antibiotic resistant bacteria is a rising problem world-wide. Infections that usedto be easily treatable have now become somehow cumbersome to cure due to treatment failurecaused by infections with antibiotic resistant bacteria. It is estimated that by 2050 approximately 10 million people will die annually due to infections with these hard-to-treat bacteria.Therefore, we need to focus our efforts on addressing this problem.

One way of addressing the problem is by developing novel antibiotics. However, since many ofthe large pharmaceutical companies have left research on antibiotic development, due to highexpenses and low profit, we are currently in an antibiotic innovation gap. Therefore, we mustturn to alternative approaches. One of these approaches could be the use of antibiotic adjuvants,also known as resistance breakers or helper compounds. The advantage of using antibiotic adjuvants is that they can extend the life of antibiotics either by directly or indirectly inhibit themechanism of antibiotic resistance thus enhancing the effect of an antibiotic, or by stimulationof host immune system.

 A newly identified antibiotic/adjuvant combination is the antibiotic bacitracin and the cannabinoid cannabidiol. Bacitracin acts on cell wall biosynthesis by inhibiting recycling of the membrane bound lipid carrier that transports peptidoglycan precursors across the membrane. Cannabidiol has been shown to synergize with bacitracin against Gram-positive pathogenic bacteria such as Staphylococcus aureus, Listeria monocytogenes and Enterococcus faecalis, in vitro.Furthermore, the combination has shown to clear a Staphylococcus aureus skin infection in amouse skin infection model, to a higher extent than either of the compounds alone. Even thoughthe exact mechanism of action of the cannabidiol mediated potentiation of bacitracin remainsunknown, our research suggests that the membrane potential disruptive effects of cannabidiolplays a key part in it. For Staphylococcus aureus to compensate for the disastrous effects of losing the electrical membrane potential, it increases the level of menaquinone, also known as vitamin K2, thus allowing it to maintain the proton motive force and hence ATP biosynthesis. Indoing so, the level of important metabolites for synthesis of the membrane bound lipid carrier,which is important for peptidoglycan biosynthesis, might be decreased and thus enhancing theeffect of bacitracin.
Translated title of the contributionKombination af cannabidiol og bacitracin mod bakterielle infektioner
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
  • Klitgaard, Janne Kudsk, Principal supervisor
  • Pontoppidan, Steen Plesner, Co-supervisor, External person
External participants
Date of defence20. Dec 2021
Publication statusPublished - 20. Dec 2021


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