期刊
CELL HOST & MICROBE
卷 10, 期 2, 页码 158-164出版社
CELL PRESS
DOI: 10.1016/j.chom.2011.07.004
关键词
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资金
- United States National Institutes of Health (NIH) [U54 AI057157, T32 HL094296-02, 5 T32 CA009582-23]
- Southeastern Regional Center of Excellence for Emerging Infections and Biodefense [R01AI069233, R01AI073843, 1 R01GM62112]
- American Heart Association
- Canadian Institutes of Health Research
- Public Health Service [T32 GM07347]
- Vanderbilt NSF-REU [CHE 0850976]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1156922] Funding Source: National Science Foundation
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.
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