Antimicrobial action of calprotectin that does not involve metal withholding

Angelique N. Besold, Edward M. Culbertson, Lily Nam, Ryan Hobbs, Alisa Boyko, C. Noel Maxwell, Walter J. Chazin, Adriana R. Marques, Valeria C. Culotta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Calprotectin is a potent antimicrobial that inhibits the growth of pathogens by tightly binding transition metals such as Mn and Zn, thereby preventing their uptake and utilization by invading microbes. At sites of infection, calprotectin is abundantly released from neutrophils, but calprotectin is also present in non-neutrophil cell types that may be relevant to infections. We show here that in patients infected with the Lyme disease pathogen Borreliella (Borrelia) burgdorferi, calprotectin is produced in neutrophil-free regions of the skin, in both epidermal keratinocytes and in immune cells infiltrating the dermis, including CD68 positive macrophages. In culture, B. burgdorferi's growth is inhibited by calprotectin, but surprisingly, the mechanism does not involve the classical withholding of metal nutrients. B. burgdorferi cells exposed to calprotectin cease growth with no reduction in intracellular Mn and no loss in activity of Mn enzymes including the SodA superoxide dismutase. Additionally, there is no obvious loss in intracellular Zn. Rather than metal depletion, we find that calprotectin inhibits B. burgdorferi growth through a mechanism that requires physical association of calprotectin with the bacteria. By comparison, calprotectin inhibited E. coli growth without physically interacting with the microbe, and calprotectin effectively depleted E. coli of intracellular Mn and Zn. Our studies with B. burgdorferi demonstrate that the antimicrobial capacity of calprotectin is complex and extends well beyond simple withholding of metal micronutrients.

Original languageEnglish (US)
Pages (from-to)1728-1742
Number of pages15
JournalMetallomics
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2018

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Leukocyte L1 Antigen Complex
Metals
Pathogens
Escherichia coli
Growth
Macrophages
Cell culture
Nutrients
Transition metals
Bacteria
Skin
Enzymes
Neutrophils
Association reactions
Lyme Disease
Micronutrients
Dermis
Infection
Keratinocytes
Superoxide Dismutase

All Science Journal Classification (ASJC) codes

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Besold, A. N., Culbertson, E. M., Nam, L., Hobbs, R., Boyko, A., Maxwell, C. N., ... Culotta, V. C. (2018). Antimicrobial action of calprotectin that does not involve metal withholding. Metallomics, 10(12), 1728-1742. https://doi.org/10.1039/c8mt00133b
Besold, Angelique N. ; Culbertson, Edward M. ; Nam, Lily ; Hobbs, Ryan ; Boyko, Alisa ; Maxwell, C. Noel ; Chazin, Walter J. ; Marques, Adriana R. ; Culotta, Valeria C. / Antimicrobial action of calprotectin that does not involve metal withholding. In: Metallomics. 2018 ; Vol. 10, No. 12. pp. 1728-1742.
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Besold, AN, Culbertson, EM, Nam, L, Hobbs, R, Boyko, A, Maxwell, CN, Chazin, WJ, Marques, AR & Culotta, VC 2018, 'Antimicrobial action of calprotectin that does not involve metal withholding', Metallomics, vol. 10, no. 12, pp. 1728-1742. https://doi.org/10.1039/c8mt00133b

Antimicrobial action of calprotectin that does not involve metal withholding. / Besold, Angelique N.; Culbertson, Edward M.; Nam, Lily; Hobbs, Ryan; Boyko, Alisa; Maxwell, C. Noel; Chazin, Walter J.; Marques, Adriana R.; Culotta, Valeria C.

In: Metallomics, Vol. 10, No. 12, 01.12.2018, p. 1728-1742.

Research output: Contribution to journalArticle

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AU - Besold, Angelique N.

AU - Culbertson, Edward M.

AU - Nam, Lily

AU - Hobbs, Ryan

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AU - Maxwell, C. Noel

AU - Chazin, Walter J.

AU - Marques, Adriana R.

AU - Culotta, Valeria C.

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Besold AN, Culbertson EM, Nam L, Hobbs R, Boyko A, Maxwell CN et al. Antimicrobial action of calprotectin that does not involve metal withholding. Metallomics. 2018 Dec 1;10(12):1728-1742. https://doi.org/10.1039/c8mt00133b