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

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


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Female
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Immunity, Innate / drug effects*
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peptides, Cyclic / pharmacology*
  • Quorum Sensing / drug effects*
  • Rabbits
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Virulence / drug effects


  • Peptides, Cyclic
  • apicidin