Antibacterial and Antibiofilm Properties of Native Australian Plant Endophytes against Wound-Infecting Bacteria

The wound management field faces significant challenges due to antimicrobial resistance (AMR) and the complexity of chronic wound care. Effective wound treatment requires antimicrobial dressings to prevent bacterial infections. However, the rise of AMR necessitates new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against <i>S. aureus</i>. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive <i>S. aureus</i> ATCC 25923 (MIC = 78.1 µg/mL) and MRSA M180920 (MIC = 78.1 µg/mL). DNA sequence analysis was employed for fungal identification. The most active sample, EL 19 (<i>Chaetomium globosum</i>), was selected for further analysis, revealing that its EtOAc extracts reduced <i>S. aureus</i> ATCC 25923 biofilm formation by 55% and cell viability by 57% to 68% at 12 × MIC. Furthermore, cytotoxicity studies using the brine shrimp lethality test demonstrated low cytotoxicity up to 6 × MIC (25% mortality rate) with an LC50 value of 639.1 µg/mL. Finally, the most active sample was incorporated into polycaprolactone (PCL) fiber mats via electrospinning, with resultant inhibition of <i>S. aureus</i> species. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.