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Fungal pathogenesis

Good cop(per), bad cop(per)

Nature Reviews Microbiology volume 13, page 3 (2015)Cite this article

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Copper is required for virulence of the fungus Cryptococcus neoformans, but an excess of this metal can have an antimicrobial effect. Interestingly, C. neoformans must disseminate from the lungs (which have high copper levels) to the brain (which has low copper levels) where it causes lethal meningoencephalitis. Now, Sun, Ju, et al. show that two copper importers, Ctr1 and Ctr4, influence fungal survival at these two sites. They found that Ctr1 is rapidly degraded in the presence of high copper levels, and in agreement with this, deletion of CTR1 had no impact on fungal virulence in mouse lungs. By contrast, deleting CTR4 resulted in a hypervirulent phenotype. Furthermore, overexpressing CTR1 or CTR4 reduced fungal survival in the lungs, which suggests that high levels of copper in this organ are toxic to C. neoformans. By contrast, CTR1 and CTR4 were necessary for fungal replication in the mouse brain, suggesting that copper import is essential for C. neoformans survival in this environment. These data suggest that C. neoformans can sense copper levels and modulate the expression of Ctr1 and Ctr4 to switch from copper detoxification to copper acquisition as it disseminates from the lungs to the brain.

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References

  1. Sun, T. -S., Ju, X., et al. Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis. Nature Commun. 5, 5550 (2014)

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  1. Cláudio Nunes-Alves
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Nunes-Alves, C. Good cop(per), bad cop(per). Nat Rev Microbiol 13, 3 (2015). https://doi.org/10.1038/nrmicro3413

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