Mechanism of berberine hydrochloride interfering with biofilm formation of Hafnia alvei

The mechanism of berberine hydrochloride (BBH) inhibiting the biofilm formation of Hafnia alvei was investigated in this study. The antibiofilm potential of BBH was evaluated by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) as well as crystal violet staining. The quorum-sensing (QS) inhibition was revealed by determination of QS-related genes expression and related signal molecules production using real-time quantitative PCR (RT-qPCR) and high performance liquid chromatography (HPLC). The binding of BBH to receptor proteins was simulated by molecular docking and molecular dynamics simulations. It was found that BBH at sub-minimum inhibitory concentrations (sub-MICs) significantly reduced the biofilm formation of H. alvei in a dose dependent manner. BBH inhibited the bacterial swimming motility, decreased the transcription of halI and halR genes, and reduced the production of signal molecule C14-HSL. It bound to HalR protein mainly through Van der Waals force and electrostatic interaction force. Based on these results, it was concluded that BBH inhibits the biofilm formation of H. alvei and the mechanism is related to its interference with QS through down-regulating the expression of halI and halR genes.