Antibiofilm activity of berberine inhibition Staphylococcus aureus

Abstract Berberine, a naturally occurring isoquinoline alkaloid, has demonstrated strong antibiofilm properties against Staphylococcus aureus (S. aureus). However, there is limited understanding of how berberine inhibits S. aureus biofilm formation and what molecular pathways berberine acts on S. aureus biofilm. Therefore, a deep understanding of berberine's inhibitory effect on S. aureus biofilm formation may provide meaningful insights for utilizing berberine in managing infections associated with S. aureus biofilms. Herein, we assessed the effect of berberine on S. aureus biofilms formation and its potential molecular pathway. XTT analysis revealed that berberine (32 μg/mL) reduced the metabolic function of S. aureus biofilms. Images obtained using the ImageXpress Micro High Content Screening System (HCS) showed that berberine effectively reduced the volume and thickness of S. aureus biofilms. Molecular fluorescence probe technology was employed to quantitatively assess the biofilm matrix components of S. aureus, and the results indicated that the levels of polysaccharide intercellular adhesin (PIA) and protein were significantly decreased by berberine. Furthermore, transcriptome sequencing and bioinformatics analysis determined that srrA in the two-component system pathway was a key regulatory target. This key gene regulates biofilms formation, possibly by affecting PIA synthesis. Our findings demonstrate that the berberine significantly inhibits S. aureus biofilms formation, providing insight for further exploration and development of effective treatments against S. aureus biofilms.