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Article
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PubMed Central
Other literature type . 2020
Data sources: PubMed Central
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Nature Chemical Biology
Article . 2020 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

Authors: Leila Lo Leggio; Aaron D. Smith; Søren Brander; Lisa N. Kinch; Dennis J. Thiele; Nick V. Grishin; Chen Ding; +9 Authors

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

Abstract

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.

Keywords

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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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
79
Top 1%
Top 10%
Top 1%
Green
hybrid