Multimodal Inhibition of Pectobacterium brasiliense Virulence by the Citrus Flavanone Naringenin

Naringenin, a flavanone from citrus, was studied for its ability to reduce virulence in Pectobacterium, a phytopathogen causing soft rot disease in crop plants. Naringenin downregulated quorum sensing (QS) and suppressed critical virulence determinants in Pectobacterium brasiliense Pb1692, including plant cell wall-degrading enzymes, bacterial motility, and biofilm formation, consequently reducing disease symptoms in two host plants. Molecular docking simulations revealed a plausible binding mode for naringenin within the QS protein ExpI, which were maintained during microsecond-long Molecular Dynamics simulations. These simulations provided atomic-scale insight into specific interactions and estimated binding free energies, supporting naringenin's QS inhibition mode of action. In contrast, S-adenosyl methionine, the natural ligand of ExpI, was unable to maintain a stable binding mode in the ExpI site during simulations. Beyond QS disruption, naringenin induced reactive oxygen species accumulation and compromised DNA repair, indicating a multimodal mechanism of action. Despite these promising findings, naringenin's limited aqueous solubility challenges practical applications.