Arcopilins: A New Family of Staphylococcus aureus Biofilm Disruptors from the Soil Fungus Arcopilus navicularis .

Biofilms represent a key challenge in the treatment of microbial infections; for instance, Staphylococcus aureus causes chronic or fatal infections by forming biofilms on medical devices. Herein, the fungus Arcopilus navicularis was found to produce a novel family of PKS-NRPS metabolites that are able to disrupt preformed biofilms of S. aureus . Arcopilins A-F ( 1 - 6 ), tetramic acids, and arcopilin G ( 7 ), a 2-pyridone, were elucidated using HR-ESI-MS and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Their absolute configuration was established by the synthesis of MPTA-esters for 2 , analysis of 1 H- 1 H coupling constants, and ROESY correlations, along with comparison with the crystal structure of 7 . Arcopilin A ( 1 ) not only effectively disrupts preformed biofilms of S. aureus but also potentiates the activity of gentamicin and vancomycin up to 115- and 31-fold times, respectively. Our findings demonstrate the potential application of arcopilins for the conjugated treatment of infections caused by S. aureus with antibiotics unable to disrupt preformed biofilms.