Exploring the Anti-Adherence Potential of Skt35 to Combat Catheter-Associated Staphylococcus aureus Infections: Efficacy, Toxicity and Mechanism of Action

Catheter-associated urinary tract infections (CAUTIs), often caused by biofilm-forming Staphylococcus aureus, present significant clinical challenges. Skt35, a dioxopiperidinamide derivative of cinnamic acid, was investigated for its potential antibacterial and antibiofilm activities against S. aureus biofilms. The antibacterial effect of Skt35 was assessed using the zone of inhibition and microdilution methods, revealing a minimum inhibitory concentration (MIC) of 250 mu M. Antibiofilm properties were confirmed through crystal violet assays, scanning electron microscopy and confocal laser scanning microscopy, showing significant biofilm inhibition at the Sub-MIC. In an in vitro bladder model, Skt35-coated silicone catheter tubes exhibited significant antiadhesive effects. Zebrafish embryo tests indicated no toxicity at concentrations up to 125 mu M. Molecular docking and simulation analysis revealed strong binding affinities of Skt35 to Accessory Gene Regulator A (-7.9 kcal/mol) and Lux Small protein (-4.96 kcal/mol), suggesting potential disruption of quorum sensing and gene expression in S. aureus, making it a promising candidate for catheter coatings to prevent CAUTIs.