Oxirapentyn A, Derived from Marine Amphichorda felina, Effectively Inhibits Quorum Sensing and Biofilm Formation...

The emergence of multidrug-resistant Chromobacterium violaceum, an opportunistic pathogen, poses a significant threat to human, animal, and environmental health, underscoring the urgent need for innovative strategies. Marine-derived natural compounds have gained attention as a promising source of quorum sensing inhibitors (QSIs) that can attenuate C. violaceum virulence without inducing resistance. This study reports, for the first time, the anti-quorum sensing (anti-QS) and anti-biofilm activities of oxirapentyn A, one marine natural compound, against C. violaceum. Results demonstrate oxirapentyn A (200 μg/mL) significantly inhibits biofilm formation, violacein production, and hemolysin synthesis by 48.8, 21.7, and 22.3%, respectively. Scanning electron microscopy (SEM) further corroborated the disruption of biofilm architecture. LC-MS analysis revealed a concentration-dependent reduction in the production of N-decanoyl-homoserine lactone (C₁₀-HSL), a key QS signaling molecule. Furthermore, RT-qPCR analysis indicated oxirapentyn A downregulated critical QS-related genes (cviI, cviR, vioA, chiA, and pykF) by 20.7, 36.6, 31.1, 66.6, and 30.7%, respectively. Notably, in vivo experiments demonstrated that oxirapentyn A significantly improved the survival of Galleria mellonella larvae infected with C. violaceum. Collectively, these findings highlight oxirapentyn A as a novel QSI with dual anti-QS and biofilm-disrupting activities, offering a promising strategy to combat drug-resistant bacterial infections.