Phytochemical-mediated disruption of Staphylococcus aureus biofilm by Tecomella undulata, Dalbergia sissoo, Heliotropium indicum, and Solanum virginianum extracts via targeting extracellular matrix.

Ethnomedicinal use of Tecomella undulata (Rohida) bark to treat syphilis and skin infections, Dalbergia sissoo (Sheesham) leaves/wood to cure skin infections and gonorrhoea, Heliotropium indicum (Indian heliotrope) to cure wounds; and Solanum virginianum (Kantakari) roots/fruits to relieve urinary tract infections are well known. Such conditions are associated with the Staphylococcus aureus infection, a human pathogenic bacteria known for its virulence, antibiotic resistance and biofilm forming abilities. Despite the traditional relevance of these plants, detailed scientific studies on antibiofilm activity against S. aureus remains unexplored. In this study, plant/leaf extracts of these plants were evaluated for antimicrobial activity and their underlying antibiofilm mechanism. Crude extracts (n-hexane, ethyl acetate, acetone, methanol) were analyzed and antibiofilm properties were accessed via liquid and solid-phase assays and FE-SEM. LC-HRMS identified phytochemicals were further analyzed targeting S. aureus proteins ClfA, ClfB, SrtA, SarA and AgrA via molecular docking and dynamics studies. Out of 16 crude extracts, methanolic extracts demonstrated the highest antibacterial activity with lowest MIC of TU-MeOH (1.8 mg/mL) and highest SV-MeOH (7.5mg/mL). All extracts exhibited robust biofilm inhibition (conc. 5-12.5 mg/mL) confirmed by wrinkled, non-mucoid colonies and FE-SEM showing disrupted extracellular matrix. LC-HRMS analysis of TU-MeOH revealed a total of 104 phytochemicals, including flavonoids, alkaloids, terpenoids, phenols etc. Molecular docking showed Catechin 5-O-(2-feruloyl-6-p-coumaroyl-beta-D-glucopyranoside), Goyaglycoside g and Tryptophol [xylosyl-(1->6)-glucoside] as multitargeting hits further validated by molecular dynamics showing stable interactions. Methanolic extracts of T. undulata, D. sissoo, H. indicum, and S. virginianum inhibits S. aureus biofilm disrupting the extracellular matrix. Catechin derivatives, Goyaglycoside g, and Tryptophol, act as multitarget inhibitors of key adhesive and regulatory biofilm proteins highlighting their therapeutic potential.