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

## TL;DR

This study discovers compounds from an African fungus that effectively inhibit Staphylococcus aureus biofilms, which are a major cause of persistent infections.

## Contribution

The study identifies dimeric aristolane-type sesquiterpenoids from Neonothopanus nambi as novel anti-biofilm agents against S. aureus.

## Key findings

- Aurisin B inhibits S. aureus biofilm formation by over 70% at 1 µg/mL.
- Confocal microscopy confirms the anti-biofilm effects of aurisins D and B.
- Dimerization and hydroxylation enhance the antibiofilm activity of the compounds.

## 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.

This study describes the isolation and characterization of potent bioactive compounds from the fungal strain Neonothopanus nambi, followed by structural elucidation. The compounds shown are dimeric aristolane‐type sesquiterpenoids, identified as aurisins D (1) and B (2). Antibiofilm assays against Staphylococcus aureus demonstrate significant inhibition of biofilm formation by compounds 1 and 2 at concentrations of 2 µg/mL and 1 µg/mL, respectively. Confocal laser scanning microscopy provides visual evidence supporting the antibiofilm activity of these bioactive compounds.