Targeting Staphylococcus aureus Biofilms Through Aurisin Derivatives From Neonothopanus nambi of African Origin

Biofilm formation is a key survival strategy among microorganisms and a major factor contributing to chronic and treatment-resistant infections. Staphylococcus aureus is a key biofilm-forming pathogen associated with persistent and life-threatening infections. As part of our ongoing search for novel anti-biofilm agents from Basidiomycota of tropical rainforests, we investigated the metabolome of the African fungus Neonothopanus nambi. This study led to the isolation of four dimeric aristolane-type sesquiterpenoids, aurisins D, B, A, and G (1-4), along with two monomeric sesquiterpenoids, nambinone C (5) and axinysone B (6), and methyl 4-butyramidobenzoate (7). All compounds were assessed for their antimicrobial and cytotoxic activities, as well as their ability to inhibit and eradicate S. aureus biofilms. The dimeric sesquiterpenoids (1-4) exhibited potent antibiofilm effects, with aurisin B (2) inhibiting biofilm formation by over 70% at a concentration of 1 µg/mL, well below its minimum inhibitory concentration. Confocal laser scanning microscopy further confirmed the pronounced anti-biofilm effects of aurisins D and B (1 and 2). Structure-activity relationship analysis suggests that both dimerization and hydroxylation contribute to enhanced activity. Despite some cytotoxic effects, these dimeric aristolane-type sesquiterpenoids from N. nambi represent promising leads for the development of novel anti-infective strategies targeting S. aureus biofilms, with potential applications beyond systemic use.