Prenylated Diresorcinols Inhibit Bacterial Quorum Sensing

Current treatment options for bacterial
infections are dependent
on antibiotics that inhibit microbial growth and viability. These
approaches result in the evolution of drug-resistant strains of bacteria.
An anti-infective strategy that is less likely to lead to the development
of resistance is the disruption of quorum sensing mechanisms, which
are involved in promoting virulence. The goal of this study was to
identify fungal metabolites effective as quorum sensing inhibitors.
Three new prenylated diresorcinols (1–3), along with two known compounds, (4R)-regiolone and decarboxycitrinone, were isolated from a freshwater
fungus (Helotiales sp.) from North Carolina. Their structures were
assigned on the basis of HRESIMS and NMR experiments. The structure
of compound 1 was confirmed via X-ray diffraction analysis,
and its absolute configuration was established by TDDFT-ECD and optical
rotation calculations. Compounds 1–3 suppressed quorum sensing in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with IC50 values
ranging from 0.3 to 12.5 μM. These compounds represent potential
leads in the development of antivirulence therapeutics.