Ethanol extract of Trichoderma harzianum spores exhibits antibacterial activity against Staphylococcus aureus coupled with free radical scavenging.

Fungal-derived metabolites are emerging as promising alternatives to conventional antibiotics, particularly against drug-resistant pathogens. Here, we report the Trichoderma harzianum spores ethanolic extract (THE) as a potent antibacterial agent targeting clinically relevant Staphylococcus aureus (S. aureus). THE exhibits significant antibacterial effects against S. aureus at minimal concentrations (MIC = 2.5 mg/mL) and effectively disrupts preformed biofilm. Gas chromatography-mass spectrometry (GC-MS) analysis identified 24 bioactive constituents, with steroids, fatty acids, and pyranones as the predominant antibacterial compounds. Mechanistic studies reveal that THE compromises bacterial membrane integrity, leading to increased permeability, leakage of alkaline phosphatase, and efflux of cytoplasmic proteins and DNA. Furthermore, THE demonstrates potent free radical scavenging activity, suggesting concurrent antioxidant properties. These findings suggest that the possesses both antibacterial and antioxidant activities, which may be useful for the development of antibacterial materials for medical device applications.