Metal chelation and inhibition of bacterial growth in tissue abscesses.
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.
Corbin
Brian D
BD
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Seeley
Erin H
EH
Raab
Andrea
A
Feldmann
Joerg
J
Miller
Michael R
MR
Torres
Victor J
VJ
Anderson
Kelsi L
KL
Dattilo
Brian M
BM
Dunman
Paul M
PM
Gerads
Russell
R
Caprioli
Richard M
RM
Nacken
Wolfgang
W
Chazin
Walter J
WJ
Skaar
Eric P
EP
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
D002614:Chelating Agents; D039841:Leukocyte L1 Antigen Complex; D008345:Manganese; D015032:Zinc; D002118:Calcium