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The transcriptomic and phenotypic response of the melanized yeast Exophiala dermatitidis to ionizing particle exposure

ABSTRACT: The yeast E. dermatitidis is highly resistant to ionizing particle irradiation, and exposure to this stress elicits a transcriptomic response that is distinct from that induced by photonic irradiation. Melanin, in this organism, does not exhibit substantial control over this transcriptomic response, nor does it protect the cells from radiation-induced death under the conditions we tested. However, the strong response we observed here at the gene expression level inprovides insights into the unique types of damage that particle irradiation causes to fungal cells, allowing for future dissection of radiation source-specific resistance mechanisms.

ORGANISM(S): Exophiala dermatitidis

PROVIDER: GSE152116 | GEO | 2020/06/10

REPOSITORIES: GEO

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Project description:Background: Ionizing Radiation (IR) is a known pro-inflammatory agent and in the process of development of biomarkers for radiation biodosimetry a chronic inflammatory disease condition could act as a confounding factor. Hence, it is important to develop radiation biodosimetry that can distinguish between IR-induced inflammatory responses and pre-existing disease. In this study, we compared the gene expression response of a genetically modified mouse model of inflammatory bowel disease (Il10-/-) with that of a normal wild-type mouse to potentially develop transcriptomic based biodosimetry markers for individual susceptibility to radiation. Results: Wild-type (WT) and Il10-/- mice were exposed to whole body irradiation of 7Gy (LD50/30 for IL10-/-) X-rays. Gene expression responses were studied using high throughput whole genome microarrays in peripheral blood after 24h post-irradiation. Analysis resulted in identification of 1962 and 1844 genes differentially expressed (p < 0.001, FDR < 10%) after radiation exposure in Il10-/- and WT mice respectively. A set of 155 genes were also identified as differentially expressing between WT and Il10-/- mice at the baseline pre-irradiation level. Gene ontology analysis revealed that the baseline differentially expressing genes (155) were mainly involved in Inflammatory response, Glutathione metabolism and fibrosis. Analysis of radiation responsive genes revealed commonality of immune function genes between WT and Il10-/- mice. Gene ontology analysis revealed that innate immune response and p53 signaling processes were strongly associated with up-regulated genes whereas, B-cell development process was found to be significant amongst downregulated genes in response to radiation in the two genotypes. However, specific immune response pathways like MHC class I antigen presentation and response to viral/bacterial infection were particularly associated with radiation responsive genes of Il10-/- mice but not with WT mice. Further analysis of activation status of specific canonical pathways and upstream regulators using IPA-prediction tool revealed significant difference in the activation status of T-cell and hormone mediated signaling as well as regulators of inflammation between WT and Il10-/- after irradiation.

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The transcriptomic and phenotypic response of the melanized yeast Exophiala dermatitidis to ionizing particle exposure

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