HU-210 Inhibits "Universal Autoinducer" Mediated Quorum Sensing of Vibrio harveyi.

Objectives: Cannabinoids have been studied extensively for their anti-microbial effects, but their mode of action still remains elusive. Aim of this study is to investigate if synthetic cannabinoid (HU-210) can affect Quorum Sensing (QS), a process of bacterial communication based on signal molecules. Vibrio harveyi was used as a model organism to study the effect of HU-210.
Methods: V. harveyi WT and strains mutated in the QS cascade (BB120, BB152 & MM30) were grown (planktonic) overnight at 30ºC in AB+ media in the presence of different sub-MIC concentrations of HU-210. Changes in bio-luminescence (representing QS) and growth (OD, λ=595nm) were recorded during incubation every half an hour. The biofilm was generated in AB+ media in the presence of different concentrations of HU-210 for 24 hours. The biofilm biomass was quantified using crystal violet and DNA quantification method. Bacterial motility assays were performed using semi-solid agar plates (0.18% agar plates with different HU-210 concentrations). Plates were incubated for 18 hours and motility halos were quantified and compared using Image J Software.
Results: HU-210 reduced QS regulated bio-luminescence of BB152 strain ( AI-1^-) up to 90% in dose dependent manner while it didn’t show any effect on bacterial growth and QS of other tested strains. qPCR method showed a significant decrease (about 75%) in biofilm biomass of BB152 strain in the presence of HU-210, compared to control. HU-210 significantly reduced motility of all the tested strains.



Conclusions: Our results suggest that HU-210 decreases notably AI-2 dependent quorum sensing of V. harveyi resulting in suppressed bioluminescence, ability to form biofilm and swimming motility of BB152 strain. Our results indicate a novel mode of action for synthetic cannabinoids on signal transduction systems used by bacteria. HU-210 or other cannabinoids derivatives can be potential active agents in pharmaceutical preparations against dental diseases.