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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.

Publication ,  Journal Article
Garcia-Santamarina, S; Probst, C; Festa, RA; Ding, C; Smith, AD; Conklin, SE; Brander, S; Kinch, LN; Grishin, NV; Franz, KJ; Riggs-Gelasco, P ...
Published in: Nature chemical biology
March 2020

Infection by the fungal pathogen Cryptococcus neoformans causes lethal meningitis, primarily in immune-compromised individuals. Colonization of the brain by C. neoformans is dependent on copper (Cu) acquisition from the host, which drives critical virulence mechanisms. While C. neoformans Cu+ import and virulence are dependent on the Ctr1 and Ctr4 proteins, little is known concerning extracellular Cu ligands that participate in this process. We identified a C. neoformans gene, BIM1, that is strongly induced during Cu limitation and which encodes a protein related to lytic polysaccharide monooxygenases (LPMOs). Surprisingly, bim1 mutants are Cu deficient, and Bim1 function in Cu accumulation depends on Cu2+ coordination and cell-surface association via a glycophosphatidyl inositol anchor. Bim1 participates in Cu uptake in concert with Ctr1 and expression of this pathway drives brain colonization in mouse infection models. These studies demonstrate a role for LPMO-like proteins as a critical factor for Cu acquisition in fungal meningitis.

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Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

March 2020

Volume

16

Issue

3

Start / End Page

337 / 344

Related Subject Headings

  • Virulence
  • Polysaccharides
  • Mixed Function Oxygenases
  • Mice, Inbred A
  • Mice
  • Meningitis
  • Fungal Proteins
  • Female
  • Disease Models, Animal
  • Cryptococcus neoformans
 

Citation

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Garcia-Santamarina, S., Probst, C., Festa, R. A., Ding, C., Smith, A. D., Conklin, S. E., … Thiele, D. J. (2020). A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis. Nature Chemical Biology, 16(3), 337–344. https://doi.org/10.1038/s41589-019-0437-9
Garcia-Santamarina, Sarela, Corinna Probst, Richard A. Festa, Chen Ding, Aaron D. Smith, Steven E. Conklin, Søren Brander, et al. “A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.Nature Chemical Biology 16, no. 3 (March 2020): 337–44. https://doi.org/10.1038/s41589-019-0437-9.
Garcia-Santamarina S, Probst C, Festa RA, Ding C, Smith AD, Conklin SE, et al. A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis. Nature chemical biology. 2020 Mar;16(3):337–44.
Garcia-Santamarina, Sarela, et al. “A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.Nature Chemical Biology, vol. 16, no. 3, Mar. 2020, pp. 337–44. Epmc, doi:10.1038/s41589-019-0437-9.
Garcia-Santamarina S, Probst C, Festa RA, Ding C, Smith AD, Conklin SE, Brander S, Kinch LN, Grishin NV, Franz KJ, Riggs-Gelasco P, Lo Leggio L, Johansen KS, Thiele DJ. A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis. Nature chemical biology. 2020 Mar;16(3):337–344.

Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

March 2020

Volume

16

Issue

3

Start / End Page

337 / 344

Related Subject Headings

  • Virulence
  • Polysaccharides
  • Mixed Function Oxygenases
  • Mice, Inbred A
  • Mice
  • Meningitis
  • Fungal Proteins
  • Female
  • Disease Models, Animal
  • Cryptococcus neoformans