Synergistic inhibition of agr quorum sensing in methicillin-resistant Staphylococcus aureus: a novel approach with natural compound encapsulation

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat due to its resistance to common antibiotics. This study investigates the antibacterial and quorum-sensing (QS) inhibitory effects of encapsulated quercetin (QE) and ferulic acid (FA) in chitosan (CS) nanoparticles against MRSA virulence genes. QE and FA were encapsulated into CS nanoparticles and characterized using scanning electron microscope, X-ray diffraction, dynamic light scattering (DLS), thermogravimetric analysis (TGA), and zeta potential analysis. Encapsulation efficiency, antibacterial activity, biofilm inhibition, hemolysis, macrophage intracellular killing, cytotoxicity, and apoptosis induction were assessed for both free and encapsulated forms. Antibacterial activity was evaluated via growth inhibition, biofilm formation assays, and minimum inhibitory concentration (MIC) determination in combination with clindamycin. RT-PCR was used to assess effects on MRSA virulence gene expression. All treatments inhibited MRSA growth, with the CS-QE-FA combination showing the highest inhibition (85) and biofilm reduction (90). This combination also synergized with clindamycin, reducing its MIC to 1/64 of the original. RT-PCR revealed significant downregulation of QS-related genes, including RNAIII, agrA, hla, and psm alpha (P < 0.001). CS nanoparticles encapsulating QE and FA significantly inhibit MRSA growth and QS-related gene expression, especially in combination. Their synergistic action with clindamycin suggests potential for novel therapeutic strategies against antibiotic-resistant infections.