Electronic properties and adjuvant effect of riparins I-IV: Inhibition of β-lactamase and QacC efflux pump in Staphylococcus aureus K4100.

Staphylococcus aureus is a leading cause of nosocomial infections, posing a significant health threat due to its resistance mechanisms, particularly involving β-lactamase enzymes and efflux pumps. Targeting these mechanisms is crucial to restore the efficacy of antibiotics. This study characterized the electronic properties of riparins I, II, III, and IV and evaluated their effects on the β-lactamase enzyme and the QacC efflux pump in the S. aureus K4100 strain. The electronic properties of the riparins revealed distinct electrophilic characteristics, but similar nucleophilic behavior, as indicated by the HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital) orbital energy values. Microbiological testing showed that riparins I, II, III, and IV did not display direct antibacterial activity against S. aureus K4100. However, riparin III significantly reduced the MIC of oxacillin, suggesting it potentiates the antibiotic's effect, likely by targeting the β-lactamase enzyme. Furthermore, riparins II and III lowered the MIC of ethidium bromide, indicating their potential as inhibitors of the QacC efflux pump. These findings highlight the potential of riparins II and III as adjuvants to enhance the effectiveness of antibiotics against multidrug-resistant strains of S. aureus.