Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways

Abstract Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naïve populations. Despite recent advances in understanding pathogenesis, host response to infection remains poorly understood. Here we modelled a total of 162 metabolite...

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Autores principales:	Laura F. Grogan, Lee F. Skerratt, Lee Berger, Scott D. Cashins, Robert D. Trengove, Joel P. A. Gummer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/450310fcf9304d47ac43f81cc3c56cbb
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spelling	oai:doaj.org-article:450310fcf9304d47ac43f81cc3c56cbb2021-12-02T15:08:26ZChytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways10.1038/s41598-018-26427-z2045-2322https://doaj.org/article/450310fcf9304d47ac43f81cc3c56cbb2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-26427-zhttps://doaj.org/toc/2045-2322Abstract Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naïve populations. Despite recent advances in understanding pathogenesis, host response to infection remains poorly understood. Here we modelled a total of 162 metabolites across skin and liver tissues of 61 frogs from four populations (three long-exposed and one naïve to the fungus) of the Australian alpine tree frog (Litoria verreauxii alpina) throughout a longitudinal exposure experiment involving both infected and negative control individuals. We found that chytridiomycosis dramatically altered the organism-wide metabolism of clinically diseased frogs. Chytridiomycosis caused catastrophic failure of normal homeostatic mechanisms (interruption of biosynthetic and degradation metabolic pathways), and pronounced dysregulation of cellular energy metabolism. Key intermediates of the tricarboxylic acid cycle were markedly depleted, including in particular α-ketoglutarate and glutamate that together constitute a key nutrient pathway for immune processes. This study was the first to apply a non-targeted metabolomics approach to a fungal wildlife disease and specifically to dissect the host-pathogen interface of Bd-infected frogs. The patterns of metabolite accumulation we have identified reveal whole-body metabolic dysfunction induced by a fungal skin infection, and these findings have broad relevance for other fungal diseases.Laura F. GroganLee F. SkerrattLee BergerScott D. CashinsRobert D. TrengoveJoel P. A. GummerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura F. Grogan Lee F. Skerratt Lee Berger Scott D. Cashins Robert D. Trengove Joel P. A. Gummer Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
description	Abstract Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naïve populations. Despite recent advances in understanding pathogenesis, host response to infection remains poorly understood. Here we modelled a total of 162 metabolites across skin and liver tissues of 61 frogs from four populations (three long-exposed and one naïve to the fungus) of the Australian alpine tree frog (Litoria verreauxii alpina) throughout a longitudinal exposure experiment involving both infected and negative control individuals. We found that chytridiomycosis dramatically altered the organism-wide metabolism of clinically diseased frogs. Chytridiomycosis caused catastrophic failure of normal homeostatic mechanisms (interruption of biosynthetic and degradation metabolic pathways), and pronounced dysregulation of cellular energy metabolism. Key intermediates of the tricarboxylic acid cycle were markedly depleted, including in particular α-ketoglutarate and glutamate that together constitute a key nutrient pathway for immune processes. This study was the first to apply a non-targeted metabolomics approach to a fungal wildlife disease and specifically to dissect the host-pathogen interface of Bd-infected frogs. The patterns of metabolite accumulation we have identified reveal whole-body metabolic dysfunction induced by a fungal skin infection, and these findings have broad relevance for other fungal diseases.
format	article
author	Laura F. Grogan Lee F. Skerratt Lee Berger Scott D. Cashins Robert D. Trengove Joel P. A. Gummer
author_facet	Laura F. Grogan Lee F. Skerratt Lee Berger Scott D. Cashins Robert D. Trengove Joel P. A. Gummer
author_sort	Laura F. Grogan
title	Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
title_short	Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
title_full	Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
title_fullStr	Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
title_full_unstemmed	Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
title_sort	chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/450310fcf9304d47ac43f81cc3c56cbb
work_keys_str_mv	AT laurafgrogan chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways AT leefskerratt chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways AT leeberger chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways AT scottdcashins chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways AT robertdtrengove chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways AT joelpagummer chytridiomycosiscausescatastrophicorganismwidemetabolicdysregulationincludingprofoundfailureofcellularenergypathways
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Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways

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