Natural phenolic compounds as novel quorum sensing inhibitors

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Authors

HELCMAN Martin MARKUŠ Juraj TREML Jakub ŠMEJKAL Karel

Year of publication 2025
Type Appeared in Conference without Proceedings
Citation
Description Quorum sensing (QS) is a communication mechanism used by unicellular organisms. Many Gram-positive and Gram-negative bacteria utilize the boron- containing molecule autoinducer 2 (AI-2) for QS, alongside species-specific signaling systems. We isolated bioactive substances from Cannabis sativa L. (Cannabaceae), including neutral cannabinoids (cannabigerol, cannabinol), cannabinoid acids (tetrahydrocannabinolic acid, cannabigerolic acid, cannabidiolic acid, cannabinolic acid), and the prenylated flavonoid cannflavin B. The biological activity of these compounds, together with other plant-derived substances such as flavonoids (including semi-synthetic imins and oxims), arylbenzofurans, furocoumarins, and xanthones, was assessed for effects on QS-regulated bioluminescence in Vibrio harveyi MM30. This mutant strain, unable to produce but still sensitive to AI-2, enabled investigation into both AI-2-dependent and independent pathways. Significant anti-QS activity was observed, notably among arylbenzofurans and semi-synthetic flavonoid derivatives, marking their first reported activity. Newly identified QS-inhibitory compounds included amorfrutin 1 from Glycyrrhiza yunnanensis, moracin M (non-prenylated arylbenzofuran), and moracin C (prenylated arylbenzofuran) from Morus alba L. Moreover, hesperetin, naringenin, and adenosine displayed strong activity for the first time in V. harveyi MM30 assays, supporting their use as affordable positive controls. Comparative analysis suggested that prenylation consistently decreased anti-QS activity across all tested classes. The effect of selected compounds on AI-2 production by methicillin-resistant Staphylococcus aureus (MRSA 7112) was evaluated using V. harveyi MM30 as a biosensor. Moracin M and cannabigerolic acid exhibited significant inhibition, highlighting their potential against MRSA. Although other compounds did not show QS-specific inhibition, amorfrutin 1, amorfrutin 2, and xanthones (toxyloxanthone C and gerontoxanthone C) demonstrated strong antibacterial properties. This study offers new perspectives on the anti-QS potential of plant-derived compounds and their relevance as bacterial communication modulators.
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