Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus

Cell Host Microbe. 2011 Aug 18;10(2):158-64. doi: 10.1016/j.chom.2011.07.004.


By sequestering manganese and zinc, the neutrophil protein calprotectin plays a crucial role in host defense against bacterial and fungal pathogens. However, the essential processes disrupted by calprotectin remain unknown. We report that calprotectin enhances the sensitivity of Staphylococcus aureus to superoxide through inhibition of manganese-dependent bacterial superoxide defenses, thereby increasing superoxide levels within the bacterial cell. Superoxide dismutase activity is required for full virulence in a systemic model of S. aureus infection, and disruption of staphylococcal superoxide defenses by calprotectin augments the antimicrobial activity of neutrophils promoting in vivo clearance. Calprotectin mutated in two transition metal binding sites and therefore defective in binding manganese and zinc does not inhibit microbial growth, unequivocally linking the antimicrobial properties of calprotectin to metal chelation. These results suggest that calprotectin contributes to host defense by rendering bacterial pathogens more sensitive to host immune effectors and reducing bacterial growth.

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
  • Anti-Bacterial Agents / immunology
  • Disease Models, Animal
  • Leukocyte L1 Antigen Complex / immunology*
  • Male
  • Manganese / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Oxidative Stress
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / enzymology*
  • Staphylococcus aureus / immunology
  • Superoxide Dismutase / metabolism*
  • Superoxides / metabolism*
  • Zinc / metabolism


  • Anti-Bacterial Agents
  • Leukocyte L1 Antigen Complex
  • Superoxides
  • Manganese
  • Superoxide Dismutase
  • Zinc