Deciphering the mechanisms of antibacterial and antibiofilm potential of phenolic compounds against Serratia marcescens

Biofilm formation significantly contributes to antibiotic resistance in Serratia marcescens, a multidrug-resistant pathogen implicated in persistent respiratory infections. This study investigates the antibacterial and anti-biofilm potential of two plant-derived phenolic acids—coumaric acid and syringic acid—against S. marcescens. Both compounds demonstrated strong inhibitory activity against planktonic cells, exhibiting low MIC values. They induced membrane permeabilization and leakage, leading to cell death, and triggered externalization of phosphatidylserine—hallmarks of apoptosis-like death in bacteria. Coumaric and syringic acids markedly inhibited biofilm formation by 70% and 80%, respectively, and efficiently disrupted mature biofilms by degrading extracellular DNA (eDNA), a key structural component of the EPS matrix. The eDNA-binding assays revealed strong interactions between the compounds and eDNA, with reduced fluorescence confirming their destabilizing effects on biofilm architecture. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) further corroborated these findings, showing disrupted biofilm structure and a predominance of dead cells in treated groups. In addition, both compounds significantly attenuated quorum sensing (QS)-regulated virulence factors and inhibited bacterial motility, including swimming and swarming, critical for biofilm propagation. These combined antibacterial, anti-biofilm, and anti-virulence effects suggest that coumaric and syringic acids act through a comprehensive mechanism disrupting both cellular integrity and intercellular communication pathways essential for S. marcescens pathogenicity. Together, these findings highlight the potential of coumaric and syringic acids as promising phytochemicals for the development of novel anti-biofilm therapeutics targeting antibiotic-resistant S. marcescens infections.