2H-chromen-2-one disrupts the Staphylococcus aureus biofilm matrix and potentiates moxifloxacin activity: In vitro and in silico analyses.

OBJECTIVES

Staphylococcus aureus biofilms contribute to antimicrobial tolerance and treatment failure, motivating the search for antibiofilm adjuvants that restore antibiotic activity. In this study, we evaluated 2H-chromen-2-one isolated from Aspidistra letrea for its antibiofilm activity and its ability to potentiate moxifloxacin (MXF) against S. aureus biofilms.

METHODS

Established biofilms were quantified by total biomass (crystal violet staining) and viable bacteria (CFU enumeration) following exposure to 2H-chromen-2-one alone or in combination with MXF, including testing MXF at a clinically relevant peak concentration (Cmax). Molecular docking was performed against proteins encoded by the ica locus to explore potential molecular targets.

RESULTS

2H-chromen-2-one reduced biofilm biomass by approximately 50% at 1-2 mg/mL and markedly increased MXF antibiofilm killing in a concentration-dependent manner. Notably, MXF alone showed minimal killing at Cmax, whereas co-treatment achieved a reduction of up to approximately 1.6 log10 CFU/mL (>97% killing) and reduced the bactericidal concentration requirement from >1.5 to 0.032 mg/L. Moreover, the maximal reduction efficacy of MXF increased from approximately -2 log10 CFU/mL when MXF was used alone to approximately -3 log10 CFU/mL when combined with 2H-chromen-2-one. Docking suggested a putative interaction between 2H-chromen-2-one and IcaC, consistent with interference in poly-N-acetylglucosamine (PNAG)-associated matrix biology.

CONCLUSIONS

Collectively, these data indicate that 2H-chromen-2-one is a promising antibiofilm adjuvant that can sensitize S. aureus biofilms to moxifloxacin, supporting its further validation in clinical isolates and in vivo models.