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 1H–1H 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.