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

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nadja B. Cech, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
Huzefa A. Raja, Postdoctoral Fellow (Creator)
Daniel A. Todd (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: 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.

Additional Information

Publication
Cell Reports, 27(1), 187-198
Language: English
Date: 2019
Keywords
Staphylococcus aureus, MRSA, quorum sensing, agr, apicidin, natural product, pathogenesis, skin infection

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