title: Metal chelation and inhibition of bacterial growth in tissue abscesses.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Corbin
authors.forename: Erin H
authors.initials: EH
authors.lastname: Seeley
authors.forename: Andrea
authors.initials: A
authors.lastname: Raab
authors.forename: Joerg
authors.initials: J
authors.lastname: Feldmann
authors.forename: Michael R
authors.initials: MR
authors.lastname: Miller
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.forename: Kelsi L
authors.initials: KL
authors.lastname: Anderson
authors.forename: Brian M
authors.initials: BM
authors.lastname: Dattilo
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Russell
authors.initials: R
authors.lastname: Gerads
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nacken
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Chazin
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D000038:Abscess / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism* / Q000494:pharmacology; D019281:Dimerization; D020869:Gene Expression Profiling; D007674:Kidney Diseases / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008100:Liver Abscess / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008345:Manganese / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D009504:Neutrophils / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D015032:Zinc / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D039841:Leukocyte L1 Antigen Complex; D008345:Manganese; D015032:Zinc; D002118:Calcium