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Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin.

Authors
  • Schilcher, Katrin1
  • Andreoni, Federica1
  • Uchiyama, Satoshi1
  • Ogawa, Taiji1
  • Schuepbach, Reto A2
  • Zinkernagel, Annelies S1
  • 1 Division of Infectious Diseases and Hospital Epidemiology.
  • 2 Division of Surgical Intensive Care Medicine, University Hospital Zurich, University of Zurich, Switzerland. , (Switzerland)
Type
Published Article
Journal
The Journal of Infectious Diseases
Publisher
Oxford University Press
Publication Date
Aug 01, 2014
Volume
210
Issue
3
Pages
473–482
Identifiers
DOI: 10.1093/infdis/jiu091
PMID: 24526740
Source
Medline
Keywords
License
Unknown

Abstract

The Gram-positive human pathogen Staphylococcus aureus causes a variety of human diseases such as skin infections, pneumonia, and endocarditis. The micrococcal nuclease Nuc1 is one of the major S. aureus virulence factors and allows the bacterium to avoid neutrophil extracellular trap (NET)-mediated killing. We found that addition of the protein synthesis inhibitor clindamycin to S. aureus LAC cultures decreased nuc1 transcription and subsequently blunted nuclease activity in a molecular beacon-based fluorescence assay. We also observed reduced NET degradation through Nuc1 inhibition translating into increased NET-mediated clearance. Similarly, pooled human immunoglobulin specifically inhibited nuclease activity in a concentration-dependent manner. Inhibition of nuclease activity by clindamycin and immunoglobulin enhanced S. aureus clearance and should be considered in the treatment of S. aureus infections.

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