Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections

PLoS Pathog. 2015 Jul 6;11(7):e1005026. doi: 10.1371/journal.ppat.1005026. eCollection 2015 Jul.


Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression. During staphylococcal encounter with murine neutrophils or staphylococcal infection of the murine peritoneal cavity, calprotectin increases the activity of the SaeRS TCS as well as the production of proinflammatory cytokines such as IL-1β and TNF-α, resulting in higher murine mortality. These results suggest that, under certain conditions, calprotectin can be exploited by S. aureus to increase bacterial virulence and host mortality.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins
  • Blotting, Western
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Host-Parasite Interactions / physiology*
  • Leukocyte L1 Antigen Complex / immunology*
  • Leukocyte L1 Antigen Complex / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Polymerase Chain Reaction
  • Protein Kinases / immunology*
  • Protein Kinases / metabolism
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / pathogenicity
  • Virulence / physiology


  • Bacterial Proteins
  • Leukocyte L1 Antigen Complex
  • Protein Kinases
  • SaeS protein, Staphylococcus aureus