Role of Calprotectin in Withholding Zinc and Copper from Candida albicans.

Besold AN, Gilston BA, Radin JN, Ramsoomair C, Culbertson EM, Li CX, Cormack BP, Chazin WJ, Kehl-Fie TE, Culotta VC
Infect Immun. 2018 86 (2)

PMID: 29133349 · PMCID: PMC5778358 · DOI:10.1128/IAI.00779-17

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 .

Copyright © 2018 American Society for Microbiology.

MeSH Terms (10)

Animals Candida albicans Copper Fungal Proteins Homeostasis Leukocyte L1 Antigen Complex Mice Mice, Inbred C57BL Mice, Knockout Zinc

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