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

ABSTRACT 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.