Abstract

Cannabigerol (CBG) is a non-psychoactive cannabinoid naturally present in trace amounts in the Cannabis plant. So far, CBG has been shown to exert diverse activities in eukaryotes. However, much less is known about its effects on prokaryotes. In this study, we investigated the potential role of CBG as an anti-biofilm and anti-quorum sensing agent against Vibrio harveyi. Quorum sensing (QS) is a cell-to-cell communication system among bacteria that involves small signaling molecules called autoinducers, enabling bacteria to sense the surrounding environment. The autoinducers cause alterations in gene expression and induce bioluminescence, pigment production, motility and biofilm formation. The effect of CBG was tested on V. harveyi grown under planktonic and biofilm conditions. CBG reduced the QS-regulated bioluminescence and biofilm formation of V. harveyi at concentrations not affecting the planktonic bacterial growth. CBG also reduced the motility of V. harveyi in a dose-dependent manner. We further observed that CBG increased LuxO expression and activity, with a concomitant 80% downregulation of the LuxR gene. Exogenous addition of autoinducers could not overcome the QS-inhibitory effect of CBG, suggesting that CBG interferes with the transmission of the autoinducer signals. In conclusion, our study shows that CBG is a potential anti-biofilm agent via inhibition of the QS cascade.

Highlights

  • Bacteria can communicate by means of signaling molecules called autoinducers (AIs) in a process called quorum sensing (QS)

  • Quorum sensing allows bacteria to switch between two distinct gene expression programs, one that is favored at low cell density (LCD) for individual, asocial behaviors, while the other is favored at high cell density (HCD) for social, group behaviors (Ng and Bassler, 2009)

  • Bacterial biofilm formation is associated with the quorum sensing process which can be critical for bacterial survival (Rutherford and Bassler, 2012)

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Summary

Introduction

Bacteria can communicate by means of signaling molecules called autoinducers (AIs) in a process called quorum sensing (QS). Quorum sensing governs several processes which are critical for bacterial survival and allows them to respond to changes in cell density (Mukherjee and Bassler, 2019) These processes include biofilm formation, virulence factor secretion, bioluminescence, motility, antibiotic production, sporulation and development of genetic competence (Singh et al, 2009). When the autoinducer concentrations are high (at high cell density), the receptors switch to phosphatases allowing for the dephosphorylation of LuxU and LuxO. This in turn results in LuxR-mediated induction of genes involved in bioluminescence and biofilm formation (Ng and Bassler, 2009; Zhang et al, 2012)

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