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Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis.

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Author

  • Tian-Shu Sun
  • Xiao Ju
  • Hui-Ling Gao
  • Tao Wang
  • Dennis J Thiele
  • Jia-Yi Li
  • Zhan-You Wang
  • Chen Ding

Summary, in English

Copper homeostasis is important for virulence of the fungus Cryptococcus neoformans, which can cause lethal meningoencephalitis in humans. Cryptococcus cells encounter high copper levels in the lung, where infection is initiated, and low copper levels in the brain. Here we demonstrate that two Cryptococcus copper transporters, Ctr1 and Ctr4, differentially influence fungal survival during pulmonary infection and the onset of meningoencephalitis. Protein Ctr1 is rapidly degraded under the high-copper conditions found in infected lungs, and its loss has no effect in fungal virulence in mice. By contrast, deleting CTR4 results in a hypervirulent phenotype. Overexpressing either Ctr1 or Ctr4 leads to profound reductions in fungal burden in the lung. However, during the onset of meningoencephalitis, expression of the copper transporters is induced and is critical for Cryptococcus virulence. Our work demonstrates that the fungal cells switch between copper detoxification and acquisition to address different copper stresses in the host.

Publishing year

2014

Language

English

Publication/Series

Nature Communications

Volume

5

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Neurosciences

Status

Published

Research group

  • Neural Plasticity and Repair

ISBN/ISSN/Other

  • ISSN: 2041-1723