Journal article
Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus
Cell host & microbe, Vol.10(2), pp.158-164
08/18/2011
DOI: 10.1016/j.chom.2011.07.004
PMCID: PMC3157011
PMID: 21843872
Abstract
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.
Details
- Title: Subtitle
- Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus
- Creators
- Thomas E. Kehl-Fie - Vanderbilt UniversitySeth Chitayat - Vanderbilt UniversityM. Indriati Hood - Vanderbilt UniversitySteven Damo - Vanderbilt UniversityNicole Restrepo - Vanderbilt UniversityCarlos Garcia - Vanderbilt UniversityKim A. Munro - Queen's UniversityWalter J. Chazin - Vanderbilt UniversityEric P. Skaar - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.10(2), pp.158-164
- Publisher
- Elsevier
- DOI
- 10.1016/j.chom.2011.07.004
- PMID
- 21843872
- PMCID
- PMC3157011
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Number of pages
- 7
- Grant note
- R01GM062112 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) CHE 0850976 / Vanderbilt NSF-REU U54 AI057157; T32 HL094296-02; 5 T32 CA009582-23 / United States National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA American Heart Association T32CA009582 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32HL094296 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) T32 GM07347 / Public Health Service; United States Department of Health & Human Services; United States Public Health Service R01AI069233; R01AI073843; 1 R01GM62112 / Southeastern Regional Center of Excellence for Emerging Infections and Biodefense; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AI073843 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR)
- Language
- English
- Date published
- 08/18/2011
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618637302771
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