Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation

PLoS One. 2013 Dec 30;8(12):e84089. doi: 10.1371/journal.pone.0084089. eCollection 2013.


Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / metabolism
  • Biofilms / growth & development*
  • Brain / microbiology*
  • Brain / surgery
  • Catheter-Related Infections / microbiology*
  • Cerebral Ventricles / microbiology
  • Cerebral Ventricles / surgery
  • Child
  • Humans
  • Inflammation / microbiology
  • Male
  • Mice
  • Mutation
  • Peptide Hydrolases / metabolism
  • Postoperative Complications / microbiology
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Bacterial Proteins
  • Bacterial Toxins
  • SarA protein, bacterial
  • Trans-Activators
  • Peptide Hydrolases