Multiomics Integrated Analysis of the Inhibitory Mechanism of Tannic Acid on MRSA Biofilms

Methicillin-resistant Staphylococcus aureus (MRSA) represents a significant threat to global public health due to its inherent antibiotic resistance and robust biofilm-forming capability. Biofilms markedly enhance bacterial resilience by impeding antibiotic penetration and evading the host immune responses. Tannic acid (TA), a naturally occurring polyphenolic compound, exhibits broad-spectrum antimicrobial and antibiofilm properties; however, the underlying mechanisms remain poorly understood. In this study, the inhibitory effects of subinhibitory concentrations of TA on MRSA biofilm formation were systematically investigated through an integrative multiomics approach (encompassing transcriptomic, proteomic, and metabolomic analyses) complemented by comprehensive phenotypic validation. Phenotypic assays demonstrated that TA effectively disrupted the biofilm architecture and reduced biofilm biomass without exerting bacteriostatic or bactericidal effects. Integrated multiomics analysis revealed that differentially expressed genes, proteins, and metabolites following TA treatment were significantly enriched in key metabolic pathways, including glycolysis/gluconeogenesis, the pentose phosphate pathway, glycerophospholipid metabolism, and glycine, serine, and threonine metabolism. Suppression of these pathways likely diminished the availability of precursors for extracellular polysaccharide synthesis and compromised the membrane lipid integrity, thereby impairing biofilm development. These findings provide a mechanistic foundation and novel insights into the potential application of TA as a therapeutic agent targeting biofilm-associated MRSA infections.