Discovery of Virulence Attenuator of Chromobacterium violaceum CV026 From Marine‐Derived Fungus Aspergillus ochraceus LSD‐13 by Inhibiting Quorum Sensing and Destroying Biofilm
Targeted quorum‐sensing (QS) represents a promising approach to combat multidrug‐resistant infections. In this study, an undescribed pyrazine derivative 5‐isobutyryl‐1,4‐dihydropyrazine‐2,3‐dione (1) together with three known compounds (2‐‐4) were isolated from the marine‐derived fungus Aspergillus ochraceus LSD‐13. Compound 2 was a potent virulence attenuator of Chromobacterium violaceum CV026 with a minimum inhibitory concentration (MIC) of 32 µg/mL. At sub‐MIC, compound 2 significantly suppressed the production of QS‐controlled phenotypes: violacein, N‐acyl homoserine lactone, chitinase, and extracellular polysaccharide. It also reduced biofilm formation by 73.3% at 1/2 MIC, a phenotype confirmed by scanning electron microscopy. Furthermore, compound 2 inhibited swarming motility in a dose‐dependent manner. Mechanistic investigations revealed that compound 2 downregulated the expression of QS‐associated genes (cviR, vioA, vioC). Molecular docking demonstrated that compound 2 has a strong binding affinity for CviR protein with −6.8 kcal/mol, suggesting a competitive antagonism of the native C6HSL ligand. These findings highlight compound 2 as a promising QS inhibitor with therapeutic potential against C. violaceum CV026.