Griffith Wildlife Disease Ecology Group, Environmental Futures Research Institute, School of Environment, Griffith University, Nathan, Queensland, 4111, Australia.
One Health Research Group, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, 4811, Australia.
Sci Rep. 2018 May 29;8(1):8188. doi: 10.1038/s41598-018-26427-z.
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.
壶菌病是近年来几种新出现的野生动物真菌病之一，这些疾病导致了一些野生动物的数量减少甚至灭绝。尽管最近在发病机制方面取得了一些进展，但宿主对感染的反应仍知之甚少。在这里，我们对来自四个种群（三个长期暴露于真菌，一个对真菌无反应）的 61 只澳大利亚高山树蛙（Litoria verreauxii alpina）的皮肤和肝脏组织中的 162 种代谢物进行了建模，这些青蛙参与了一项纵向暴露实验，包括感染组和阴性对照组的个体。我们发现，壶菌病极大地改变了临床患病青蛙的全身代谢。壶菌病导致正常的体内平衡机制（生物合成和降解代谢途径的中断）灾难性失效，并显著扰乱了细胞能量代谢。三羧酸循环的关键中间产物明显减少，包括特别重要的α-酮戊二酸和谷氨酸，它们共同构成了免疫过程的关键营养途径。这项研究首次将非靶向代谢组学方法应用于真菌野生动物疾病，并专门剖析了 Bd 感染青蛙的宿主-病原体界面。我们所确定的代谢物积累模式揭示了由真菌皮肤感染引起的全身代谢功能障碍，这些发现对其他真菌病具有广泛的相关性。
