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

Sun, Tian-Shu; Ju, Xiao; Gao, Hui-Ling; Wang, Tao; Thiele, Dennis J; Li, Jia-Yi LU ; Wang, Zhan-You and Ding, Chen (2014) In Nature Communications 5.
Abstract
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... (More)
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. (Less)
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Contribution to journal
publication status
published
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in
Nature Communications
volume
5
publisher
Nature Publishing Group
external identifiers
  • pmid:25417972
  • wos:000345913600014
  • scopus:84923295145
ISSN
2041-1723
DOI
10.1038/ncomms6550
language
English
LU publication?
yes
id
c4a94418-ebce-4c4e-a1f5-afcf9a4de4a1 (old id 4816232)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25417972?dopt=Abstract
date added to LUP
2014-12-03 17:43:31
date last changed
2017-10-01 04:20:54
@article{c4a94418-ebce-4c4e-a1f5-afcf9a4de4a1,
  abstract     = {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.},
  articleno    = {5550},
  author       = {Sun, Tian-Shu and Ju, Xiao and Gao, Hui-Ling and Wang, Tao and Thiele, Dennis J and Li, Jia-Yi and Wang, Zhan-You and Ding, Chen},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis.},
  url          = {http://dx.doi.org/10.1038/ncomms6550},
  volume       = {5},
  year         = {2014},
}