Prenylated Diresorcinols Inhibit Bacterial Quorum Sensing.
Noemi D PaguiganJosé Rivera-ChávezJustin J StempinMario AugustinovićAleksandra I NorasHuzefa A RajaDaniel A ToddKathleen D TriplettCynthia DayMario FigueroaPamela R HallNadja B CechNicholas H OberlielsPublished in: Journal of natural products (2019)
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, (4 R) -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.
Keyphrases
- methicillin resistant staphylococcus aureus
- drug resistant
- staphylococcus aureus
- high resolution
- multidrug resistant
- escherichia coli
- acinetobacter baumannii
- magnetic resonance
- biofilm formation
- pseudomonas aeruginosa
- microbial community
- ms ms
- small molecule
- high speed
- magnetic resonance imaging
- molecular dynamics
- tertiary care
- density functional theory
- solid state
- climate change
- data analysis