Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses

• Published in: Science (American Association for the Advancement of Science) Vol. 319; no. 5865; pp. 962 - 965
• Main Authors: Corbin, Brian D, Seeley, Erin H, Raab, Andrea, Feldmann, Joerg, Miller, Michael R, Torres, Victor J, Anderson, Kelsi L, Dattilo, Brian M, Dunman, Paul M, Gerads, Russell, Caprioli, Richard M, Nacken, Wolfgang, Chazin, Walter J, Skaar, Eric P
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.02.2008; The American Association for the Advancement of Science
• Subjects: Abscess - immunology; Abscess - metabolism; Abscess - microbiology; Abscesses; Animals; Antimicrobials; Bacteria; Biological and medical sciences; Biomedical research; Calcium - metabolism; Chelating Agents - metabolism; Chelating Agents - pharmacology; Chelation; Dimerization; Gene Expression Profiling; General aspects; Immunology; Infections; Kidney Diseases - immunology; Kidney Diseases - metabolism; Kidney Diseases - microbiology; Kidneys; Leukocyte L1 Antigen Complex - genetics; Leukocyte L1 Antigen Complex - metabolism; Leukocyte L1 Antigen Complex - pharmacology; Liver; Liver Abscess - metabolism; Liver Abscess - microbiology; Liver Abscess - pathology; Manganese - metabolism; Mass Spectrometry; Medical sciences; Metals; Mice; Microbial growth; Neutrophils; Neutrophils - metabolism; Rodents; Staphylococcal Infections - immunology; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus infections; Zinc - metabolism; Immune response; Growth; Abscess; Chelation; Bacteria; Natural immunity; Calprotectin; Metal
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1152449

Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn²⁺ and Zn²⁺: an activity that results in reprogramming of the bacterial transcriptome. The abscesses of mice lacking calprotectin were enriched in metal, and staphylococcal proliferation was enhanced in these metal-rich abscesses. These results demonstrate that calprotectin is a critical factor in the innate immune response to infection and define metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue.