Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4816232
- author
- Sun, Tian-Shu ; Ju, Xiao ; Gao, Hui-Ling ; Wang, Tao ; Thiele, Dennis J ; Li, Jia-Yi LU ; Wang, Zhan-You and Ding, Chen
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 5
- article number
- 5550
- 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
- 2016-04-01 14:19:37
- date last changed
- 2022-02-27 02:00:43
@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.}},
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 = {{https://lup.lub.lu.se/search/files/3912699/5465007}},
doi = {{10.1038/ncomms6550}},
volume = {{5}},
year = {{2014}},
}