Molecular insights into flavone-mediated quorum sensing interference: A novel strategy against Serratia marcescens biofilm-induced antibiotic resistance"

Antibiotic resistance poses a significant challenge in modern medicine, urging the exploration of innovative approaches to combat bacterial infections. Biofilms, complex bacterial communities encased in a protective matrix, contribute to resistance by impeding antibiotic efficacy and promoting genetic exchange. Understanding biofilm dynamics is crucial for developing effective antimicrobial therapies against antibiotic resistance. This study explores the potential of flavone to combat biofilm-induced antibiotic resistance by employing in-vitro biochemical, cell biology, and In silico (MD simulation), approaches. Flavone exhibited potent antibacterial effects with a low minimum inhibitory concentration by inducing intracellular reactive oxygen species. Flavones further inhibited the formation of biofilms by 50-60 % and disrupted the pre-formed biofilms by reducing the extracellular polysaccharide substance protective layer formed on the biofilm by 80 %. Quorum sensing (QS) plays a crucial role in bacterial pathogenicity and flavone significantly attenuated the production of QS-induced virulence factors like urease, protease, lipase, hemolysin and prodigiosin pigment in a dose-dependent manner. Further In silico molecular docking studies along with molecular dynamic simulations run for 100 ns proved the stable binding affinity of flavone with QS-specific proteins which are crucial for biofilm formation. This study demonstrates the therapeutic potential of flavone to target QS-signaling pathway to combat S. marcescens biofilms.