A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis
A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis
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.
- The University of Texas Southwestern Medical Center United States
- University of Copenhagen Denmark
- North University of China China (People's Republic of)
- Howard Hughes Medical Institute United States
- KOBENHAVNS UNIVERSITET Denmark
Virulence, Mice, Inbred A, Cryptococcosis, Article, Mixed Function Oxygenases, Fungal Proteins, Disease Models, Animal, Mice, Polysaccharides, Cryptococcus neoformans, Animals, Female, Meningitis, Copper
Virulence, Mice, Inbred A, Cryptococcosis, Article, Mixed Function Oxygenases, Fungal Proteins, Disease Models, Animal, Mice, Polysaccharides, Cryptococcus neoformans, Animals, Female, Meningitis, Copper
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