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Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.

Publication ,  Journal Article
Ding, C; Festa, RA; Chen, Y-L; Espart, A; Palacios, Ò; Espín, J; Capdevila, M; Atrian, S; Heitman, J; Thiele, DJ
Published in: Cell Host Microbe
March 13, 2013

Copper (Cu) is an essential metal that is toxic at high concentrations. Thus, pathogens often rely on host Cu for growth, but host cells can hyperaccumulate Cu to exert antimicrobial effects. The human fungal pathogen Cryptococcus neoformans encodes many Cu-responsive genes, but their role in infection is unclear. We determined that pulmonary C. neoformans infection results in Cu-specific induction of genes encoding the Cu-detoxifying metallothionein (Cmt) proteins. Mutant strains lacking CMTs or expressing Cmt variants defective in Cu-coordination exhibit severely attenuated virulence and reduced pulmonary colonization. Consistent with the upregulation of Cmt proteins, C. neoformans pulmonary infection results in increased serum Cu concentrations and increases and decreases alveolar macrophage expression of the Cu importer (Ctr1) and ATP7A, a transporter implicated in phagosomal Cu compartmentalization, respectively. These studies indicate that the host mobilizes Cu as an innate antifungal defense but C. neoformans senses and neutralizes toxic Cu to promote infection.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

March 13, 2013

Volume

13

Issue

3

Start / End Page

265 / 276

Location

United States

Related Subject Headings

  • Virulence
  • Mice
  • Metallothionein
  • Lung
  • Immunology
  • Humans
  • Fungal Proteins
  • Female
  • Cryptococcus neoformans
  • Cryptococcosis
 

Citation

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Ding, C., Festa, R. A., Chen, Y.-L., Espart, A., Palacios, Ò., Espín, J., … Thiele, D. J. (2013). Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence. Cell Host Microbe, 13(3), 265–276. https://doi.org/10.1016/j.chom.2013.02.002
Ding, Chen, Richard A. Festa, Ying-Lien Chen, Anna Espart, Òscar Palacios, Jordi Espín, Mercè Capdevila, Sílvia Atrian, Joseph Heitman, and Dennis J. Thiele. “Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.Cell Host Microbe 13, no. 3 (March 13, 2013): 265–76. https://doi.org/10.1016/j.chom.2013.02.002.
Ding C, Festa RA, Chen Y-L, Espart A, Palacios Ò, Espín J, et al. Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence. Cell Host Microbe. 2013 Mar 13;13(3):265–76.
Ding, Chen, et al. “Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.Cell Host Microbe, vol. 13, no. 3, Mar. 2013, pp. 265–76. Pubmed, doi:10.1016/j.chom.2013.02.002.
Ding C, Festa RA, Chen Y-L, Espart A, Palacios Ò, Espín J, Capdevila M, Atrian S, Heitman J, Thiele DJ. Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence. Cell Host Microbe. 2013 Mar 13;13(3):265–276.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

March 13, 2013

Volume

13

Issue

3

Start / End Page

265 / 276

Location

United States

Related Subject Headings

  • Virulence
  • Mice
  • Metallothionein
  • Lung
  • Immunology
  • Humans
  • Fungal Proteins
  • Female
  • Cryptococcus neoformans
  • Cryptococcosis