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Cell Rep. 2019 Apr 2;27(1):187-198.e6. doi: 10.1016/j.celrep.2019.03.018.

Apicidin Attenuates MRSA Virulence through Quorum-Sensing Inhibition and Enhanced Host Defense.

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Roy J. and Lucille A. Carver College of Medicine, Department of Microbiology, University of Iowa, Iowa City, IA, USA.
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
Mycosynthetix, Inc., Hillsborough, NC, USA.
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Veterans Affairs, Eastern Colorado Healthcare System, Aurora, CO, USA. Electronic address:


Recurrent epidemics of drug-resistant Staphylococcus aureus illustrate the rapid lapse of antibiotic efficacy following clinical implementation. Over the last decade, community-associated methicillin-resistant S. aureus (MRSA) has emerged as a dominant cause of infections, and this problem is amplified by the hyper-virulent nature of these isolates. Herein, we report the discovery of a fungal metabolite, apicidin, as an innovative means to counter both resistance and virulence. Owing to its breadth and specificity as a quorum-sensing inhibitor, apicidin antagonizes all MRSA agr systems in a non-biocidal manner. In skin challenge experiments, the apicidin-mediated abatement of MRSA pathogenesis corresponds with quorum-sensing inhibition at in vivo sites of infection. Additionally, we show that apicidin attenuates MRSA-induced disease by potentiating innate effector responses, particularly through enhanced neutrophil accumulation and function at cutaneous challenge sites. Together, these results indicate that apicidin treatment represents a strategy to limit MRSA virulence and promote host defense.


MRSA; Staphylococcus aureus; agr; apicidin; natural product; pathogenesis; quorum sensing; skin infection

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