Comparative genomic and transcriptomic analysis of Wangiella dermatitidis, a major cause of phaeohyphomycosis and a model black yeast human pathogen
Ontology highlight
ABSTRACT: We sequenced mRNA from Wangiella dermatitidis at two pH conditions (2.5 and 6), including three biological replicates of each sample. Examination of transcript level changes in reponse to low pH stress.
Project description:We sequenced mRNA from Wangiella dermatitidis at two pH conditions (2.5 and 6), including three biological replicates of each sample.
Project description:We determine gene expression profile for the knockout of Rv3263 (DNA Methyltransferase) and compared to wildtype M. tuberculosis. Two RNA-Seq datasets are included: wildtype (H37Rv_SS1) and knockout (delta_Rv3263)
Project description:We report the transcriptome response of Exophiala dermatitidis submitted to different temperature conditions 2 Temperature conditions (45C, 1C), 2 exposition length (1 hour, 1 week) compared to optimal condition (37C)
Project description:Black or dark brown (phaeoid) fungi cause cutaneous, subcutaneous, and systemic infections in humans. Black fungi thrive in stressful conditions such as intense light, high radiation, and very low pH. Wangiella (Exophiala) dermatitidis is arguably the most studied phaeoid fungal pathogen of humans. Here, we report our comparative analysis of the genome of W. dermatitidis and the transcriptional response to low pH stress. This revealed that W. dermatitidis has lost the ability to synthesize alpha-glucan, a cell wall compound many pathogenic fungi use to evade the host immune system. In contrast, W. dermatitidis contains a similar profile of chitin synthase genes as related fungi and strongly induces genes involved in cell wall synthesis in response to pH stress. The large portfolio of transporters may provide W. dermatitidis with an enhanced ability to remove harmful products as well as to survive on diverse nutrient sources. The genome encodes three independent pathways for producing melanin, an ability linked to pathogenesis; these are active during pH stress, potentially to produce a barrier to accumulated oxidative damage that might occur under stress conditions. In addition, a full set of fungal light-sensing genes is present, including as part of a carotenoid biosynthesis gene cluster. Finally, we identify a two-gene cluster involved in nucleotide sugar metabolism conserved with a subset of fungi and characterize a horizontal transfer event of this cluster between fungi and algal viruses. This work reveals how W. dermatitidis has adapted to stress and survives in diverse environments, including during human infections.
Project description:Reductionism assumes that causation in the physical world occurs at the micro level, excluding the emergence of macro-level causation. We challenge this reductionist assumption by employing a principled, well-defined measure of intrinsic cause-effect power-integrated information (Φ), and showing that, according to this measure, it is possible for a macro level to "beat" the micro level. Simple systems were evaluated for Φ across different spatial and temporal scales by systematically considering all possible black boxes. These are macro elements that consist of one or more micro elements over one or more micro updates. Cause-effect power was evaluated based on the inputs and outputs of the black boxes, ignoring the internal micro elements that support their input-output function. We show how black-box elements can have more common inputs and outputs than the corresponding micro elements, revealing the emergence of high-order mechanisms and joint constraints that are not apparent at the micro level. As a consequence, a macro, black-box system can have higher Φ than its micro constituents by having more mechanisms (higher composition) that are more interconnected (higher integration). We also show that, for a given micro system, one can identify local maxima of Φ across several spatiotemporal scales. The framework is demonstrated on a simple biological system, the Boolean network model of the fission-yeast cell-cycle, for which we identify stable local maxima during the course of its simulated biological function. These local maxima correspond to macro levels of organization at which emergent cause-effect properties of physical systems come into focus, and provide a natural vantage point for scientific inquiries.
Project description:ChIP-seq analysis was used to identify B. dermatitidis genes bound by the GATA transcription factor encoded by SREB during growth as yeast at 37oC
Project description:The melanized yeast Exophiala dermatitidis is resistant to many environmental stresses, and is used as a model for understanding the diverse roles of melanin in fungi. To further our understanding resistance mechanism of E. dermatitidis to acute γ-radiation exposure and whether melanin plays a role in this process, we performed RNA-seq on WT and the melanin deficient mutant Δpks1 cultures exposed to γ-radiation at the dose of 1000 Gy, which resulted in ~50% cell deaths in both strains. We observed a dramatic transcriptomic response to γ-radiation that mobilizes pathways involved in morphological development, protein degradation, and DNA repair, and is unaffected by the presence of melanin.