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Science 15 February 2008:
Vol. 319. no. 5865, pp. 962 - 965
DOI: 10.1126/science.1152449
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Reports

Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses

Brian D. Corbin,1 Erin H. Seeley,2 Andrea Raab,6 Joerg Feldmann,6 Michael R. Miller,2,3 Victor J. Torres,1 Kelsi L. Anderson,4 Brian M. Dattilo,2,3 Paul M. Dunman,4 Russell Gerads,7 Richard M. Caprioli,2 Wolfgang Nacken,5 Walter J. Chazin,2,3 Eric P. Skaar1*

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.

1 Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2 Departments of Biochemistry and Chemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3 Center for Structural Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
4 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
5 Institute for Experimental Dermatology, University of Muenster, 48149 Muenster, Germany.
6 College of Physical Science, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK.
7 Applied Speciation and Consulting, Tukwila, WA 98188, USA.

* To whom correspondence should be addressed. E-mail: eric.skaar{at}vanderbilt.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)