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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Parlet CP,Kavanaugh JS,Crosby HA,Raja HA,El-Elimat T,Todd DA,Pearce CJ,Cech NB,Oberlies NH,Horswill AR

doi

10.1016/j.celrep.2019.03.018

subject

Has Abstract

pub_date

2019-04-02 00:00:00

pages

187-198.e6

issue

1

issn

2211-1247

pii

S2211-1247(19)30325-0

journal_volume

27

pub_type

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