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

Grogan, Laura F., Skerratt, Lee F., Berger, Lee, Cashins, Scott D., Trengove, Robert D., and Gummer, Joel P.A. (2018) Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways. Scientific Reports, 8. 8188.

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Abstract

Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naive 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 naive 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 a-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.

Item ID: 54200
Item Type: Article (Research - C1)
ISSN: 2045-2322
Copyright Information: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Funders: US Fish and Wildlife Service (USFWS), IUCN Amphibian Specialist Group, Australian Research Council (ARC)
Projects and Grants: USFWS Wildlife Without Borders program, ARC FT100100375, ARC DP120100811, ARC LP110200240
Date Deposited: 20 Jun 2018 07:39
FoR Codes: 07 AGRICULTURAL AND VETERINARY SCIENCES > 0707 Veterinary Sciences > 070705 Veterinary Immunology @ 50%
06 BIOLOGICAL SCIENCES > 0602 Ecology > 060207 Population Ecology @ 50%
SEO Codes: 96 ENVIRONMENT > 9608 Flora, Fauna and Biodiversity > 960805 Flora, Fauna and Biodiversity at Regional or Larger Scales @ 50%
96 ENVIRONMENT > 9604 Control of Pests, Diseases and Exotic Species > 960405 Control of Pests, Diseases and Exotic Species at Regional or Larger Scales @ 50%
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