Journal article
Role of Calprotectin in Withholding Zinc and Copper from Candida albicans
Infection and immunity, Vol.86(2), e00779-17
02/01/2018
DOI: 10.1128/IAI.00779-17
PMCID: PMC5778358
PMID: 29133349
Abstract
The opportunistic fungal pathogen
acquires essential metals from the host, yet the host can sequester these micronutrients through a process known as nutritional immunity. How the host withholds metals from
has been poorly understood; here we examine the role of calprotectin (CP), a transition metal binding protein. When CP depletes bioavailable Zn from the extracellular environment,
strongly upregulates
and
for Zn import and maintains constant intracellular Zn through numerous cell divisions. We show for the first time that CP can also sequester Cu by binding Cu(II) with subpicomolar affinity. CP blocks fungal acquisition of Cu from serum and induces a Cu starvation stress response involving
and
superoxide dismutases. These transcriptional changes are mirrored when
invades kidneys in a mouse model of disseminated candidiasis, although the responses to Cu and Zn limitations are temporally distinct. The Cu response progresses throughout 72 h, while the Zn response is short-lived. Notably, these stress responses were attenuated in CP null mice, but only at initial stages of infection. Thus, Zn and Cu pools are dynamic at the host-pathogen interface and CP acts early in infection to restrict metal nutrients from
.
Details
- Title: Subtitle
- Role of Calprotectin in Withholding Zinc and Copper from Candida albicans
- Creators
- Angelique N Besold - Johns Hopkins UniversityBenjamin A Gilston - Vanderbilt UniversityJana N Radin - University of Illinois Urbana-ChampaignChristian Ramsoomair - Vanderbilt UniversityEdward M Culbertson - Johns Hopkins UniversityCissy X Li - Johns Hopkins UniversityBrendan P Cormack - Johns Hopkins MedicineWalter J Chazin - Vanderbilt UniversityThomas E Kehl-Fie - University of Illinois Urbana-ChampaignValeria C Culotta - Johns Hopkins University
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.86(2), e00779-17
- DOI
- 10.1128/IAI.00779-17
- PMID
- 29133349
- PMCID
- PMC5778358
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Grant note
- R01 AI101171 / NIAID NIH HHS F32 AI124506 / NIAID NIH HHS R01 AI119949 / NIAID NIH HHS R01 AI118880 / NIAID NIH HHS F31 DK111114 / NIDDK NIH HHS T32 ES007028 / NIEHS NIH HHS T32 CA009110 / NCI NIH HHS T32 ES007141 / NIEHS NIH HHS
- Language
- English
- Date published
- 02/01/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618511802771
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