Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps

J Innate Immun. 2010;2(6):576-86. doi: 10.1159/000319909. Epub 2010 Sep 10.


Neutrophils are key effectors of the host innate immune response against bacterial infection. Staphylococcus aureus is a preeminent human pathogen, with an ability to produce systemic infections even in previously healthy individuals, thereby reflecting a resistance to effective neutrophil clearance. The recent discovery of neutrophil extracellular traps (NETs) has opened a novel dimension in our understanding of how these specialized leukocytes kill pathogens. NETs consist of a nuclear DNA backbone associated with antimicrobial peptides, histones and proteases that provide a matrix to entrap and kill various microbes. Here, we used targeted mutagenesis to examine a potential role of S. aureus nuclease in NET degradation and virulence in a murine respiratory tract infection model. In vitro assays using fluorescence microscopy showed the isogenic nuclease-deficient (nuc-deficient) mutant to be significantly impaired in its ability to degrade NETs compared with the wild-type parent strain USA 300 LAC. Consequently, the nuc-deficient mutant strain was significantly more susceptible to extracellular killing by activated neutrophils. Moreover, S. aureus nuclease production was associated with delayed bacterial clearance in the lung and increased mortality after intranasal infection. In conclusion, this study shows that S. aureus nuclease promotes resistance against NET-mediated antimicrobial activity of neutrophils and contributes to disease pathogenesis in vivo.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Load / genetics
  • Bacteriolysis / genetics
  • Bacteriolysis / immunology
  • Cell-Derived Microparticles / immunology
  • Cell-Derived Microparticles / microbiology
  • Cells, Cultured
  • Extracellular Space / immunology
  • Extracellular Space / microbiology
  • Gene Expression Regulation, Bacterial
  • Humans
  • Immune Evasion / genetics
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Methicillin-Resistant Staphylococcus aureus / physiology*
  • Mice
  • Mice, Inbred Strains
  • Micrococcal Nuclease / genetics
  • Micrococcal Nuclease / metabolism*
  • Mutagenesis, Site-Directed
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Neutrophils / pathology
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / microbiology
  • Respiratory Tract Infections / physiopathology
  • Sequence Deletion / genetics
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / physiopathology


  • Micrococcal Nuclease