Integrated Metabolomic and Bioreporter Screening of Five Thai Mushroom Extracts: Exploring Antibiofilm and Biocompatibility Profiles

This study evaluated the biomedical potential of ethanolic extracts from five native Thai mushrooms, revealing distinct biological activities associated with their metabolomic profiles. Termitomyces clypeatus R. Heim demonstrated exceptional biocompatibility, effectively promoting human keratinocyte (HaCaT) proliferation without causing cytotoxicity to the cells. Its primary metabolome, rich in essential amino acids and nucleosides, supports its potential as a candidate for topical wound healing, pending further functional validation. Conversely, Lentinus squarrosulus exhibited strong antibiofilm properties and moderate direct antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, demonstrating a weak additive effect with gentamicin. Mechanistic bioreporter screening and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS) suggested that this efficacy may be associated with quorum-sensing disruption and the presence of bioactive hydroquinolones, in addition to potential genotoxic stress induction. While Schizophyllum commune displayed moderate effects, Volvariella volvacea and Thaeogyroporus porentosus exhibited high-dose cytotoxicity linked to severe oxidative stress and high organic acid content, limiting their direct high-dose biomedical applications. Ultimately, T. clypeatus R. Heim and L. squarrosulus have emerged as promising candidates that warrant further investigation for tissue regeneration and potential adjunctive anti-infective applications.