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

Nat Chem Biol. 2020 Mar;16(3):337-344. doi: 10.1038/s41589-019-0437-9. Epub 2020 Jan 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Copper / metabolism*
  • Cryptococcosis / metabolism
  • Cryptococcus neoformans / metabolism*
  • Cryptococcus neoformans / pathogenicity
  • Disease Models, Animal
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Meningitis / metabolism
  • Meningitis / physiopathology
  • Mice
  • Mice, Inbred A
  • Mixed Function Oxygenases / metabolism*
  • Polysaccharides / metabolism
  • Virulence


  • Fungal Proteins
  • Polysaccharides
  • Copper
  • Mixed Function Oxygenases