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

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

Corey P Parlet, Jeffrey S Kavanaugh, Heidi A Crosby, Huzefa A Raja, Tamam El-Elimat, Daniel A Todd, Cedric J Pearce, Nadja B Cech, Nicholas H Oberlies, Alexander R Horswill

Cell Rep. 2019 Apr 2;27(1):187-198.e6.

PMID: 30943400

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP183506663	Apicidin		183506-66-3	Price

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