Natural Phenolics Disrupt Microbial Communication by Inhibiting Quorum Sensing

Quorum sensing, a bacterial cell-to-cell communication mechanism, plays a key role in bacterial virulence and biofilm formation. Targeting quorum-sensing pathways represents a promising strategy for the development of novel antibacterial agents. This study evaluated the anti-quorum-sensing activities of 18 natural compounds, including cannabinoids, arylbenzofurans, flavonoids, caffeine, and chlorogenic acid, using the luminescent biosensor strain <i>Vibrio harveyi</i> MM30. <i>V. harveyi</i> MM30, a mutant strain deficient in the production of autoinducer-2 (AI-2) but responsive to exogenous AI-2, was used to assess the activity of test compounds on the AI-2 receptor pathway. Test compounds were incubated in AI-2-containing media, and luminescence was measured to evaluate quorum-sensing inhibition. Comparisons were made in the absence of AI-2 to determine AI-2-independent inhibitory activity. The most active compounds were further tested on methicillin-resistant <i>Staphylococcus aureus</i> (MRSA 7112) to determine their effects on AI-2 production in spent media. Among the tested compounds, the non-prenylated arylbenzofuran moracin M and the prenylated arylbenzofuran moracin C exhibited significant quorum-sensing inhibitory activity in the AI-2-mediated pathway. None of the test compounds significantly inhibited quorum sensing in the absence of AI-2. Five compounds (cannabigerol, cannabidiol, cannabigerolic acid, moracin M, and moracin C) were selected for further investigation in MRSA 7112 cultures. The spent media from MRSA 7112 cultures treated with moracin M (16, 32, 64 µg/mL) and cannabigerolic acid (16 µg/mL) showed significant inhibition of AI-2 production when transferred to <i>V. harveyi</i> MM30 cultures. Moracin M and cannabigerolic acid demonstrated potential as quorum-sensing inhibitors by targeting AI-2 production and signalling pathways in MRSA 7112 and <i>V. harveyi</i>. These findings suggest their potential for further development as antibacterial agents targeting quorum-sensing mechanisms.