Project description:The human gut is inhabited by a complex ecosystem of microorganisms, encompassing bacteria, viruses, protozoa, and fungi. Recent research has illuminated the significance of the gut fungal microbiota (mycobiota) in shaping host immunity and influencing the onset and progression of various human diseases. While most investigations into gut microbiota have centered on bacteria, accumulating evidence has underscored the role of mycobiota in the development of inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD). In this study, we present the isolation of the live Malassezia globosa strains from the intestinal mucosa of UC patients for the first time. We provide a comprehensive analysis of the characteristics and virulence of this fungus. Malassezia, primarily known to inhabit human skin, prompted us to compare the genomes, transcriptomes, and virulence of M. globosa gut isolates with those of M. globosa strains isolated from the skin. This comparative analysis aimed to discern potential niche-specific adaptations of the fungus. Our findings reveal a striking disparity in the pathogenicity of M. globosa isolated from the gut compared to its skin counterpart. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines. Additionally, transcriptome analysis indicated that gut isolates of M. globosa display heightened sensitivity to normoxia compared to their skin-isolated counterparts, suggesting adaptation to the hypoxic conditions prevalent in the intestinal mucosal environment
Project description:The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. Here we show that in barrier-impaired skin, Malassezia acquires enhanced fitness and overt growth properties. By using four distinct and complementary murine models of atopic dermatitis and ichthyosis we provide evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. These findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.
Project description:During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports microbial adaptation to alkaline pH. This cascading series of interacting proteins terminates in the proteolytic activation of the highly conserved Rim101/PacC protein, a transcription factor that mediates microbial responses that favor survival in neutral/alkaline pH growth conditions, including many mammalian tissues. We identified the putative Rim pathway proteins Rim101 and Rra1 in the human skin colonizing fungus Malassezia sympodialis. Targeted mutation of these proteins confirmed their role in M. sympodialis growth at higher pH. Additionally, comparative transcriptional analysis of the mutant strains compared to wild-type suggested mechanisms for fungal adaptation to alkaline conditions. These signaling proteins are required for optimal growth in a murine model of atopic dermatitis, a pathological condition associated with increased skin pH. Together these data elucidate both conserved and phylum-specific features of microbial adaptation to extracellular stresses.
Project description:The skin commensal yeast Malassezia is associated with several skin disorders. To establish a reference resource, we sought to determine the complete genome sequence of Malassezia sympodialis and identify its protein-coding genes. A novel genome annotation workflow combining RNA sequencing, proteomics, and manual curation was developed to determine gene structures with high accuracy.
Project description:Malassezia species are lipophilic and lipid dependent yeasts belonging to the human and animal microbiota. Typically, they are isolated from regions rich in sebaceous glands. They have been associated with dermatological diseases such as seborrheic dermatitis, tinea versicolor, atopic dermatitis, and folliculitis. Genome sequences of Malassezia globosa, Malassezia sympodialis, and Malassezia pachydermatis lack genes related to fatty acid synthesis. Here, lipid synthesis pathways of M. furfur, M. pachydermatis, M. globosa, M. sympodialis and an atypical variant of M. furfur were reconstructed using genome data and Constraints Based Reconstruction and Analysis. The metabolic reconstruction allowed us to predict variation in the fluxes of each reaction over the network to satisfy the biomass objective function. Proteomic profiling improved and validated the models through data integration. Results suggest that several mechanisms including steroid and butanoate metabolism explain the yeast’s growth under different lipid conditions. Flux differences were observed in production of riboflavin in M. furfur and the biosynthesis of glycerolipids in the atypical variant of M. furfur and Malassezia sympodialis.
Project description:The Trametes versicolor genome is predicted to encode many enzymes that can effectively degrade lignin, making it a has potentially useful application intool for biopulping and biobleaching. Poplar is an important and widely cultivated species of tree species, which isand extensively applied used in the pulping industry. However, the wood degradation mechanism of T. versicolor from transcriptomic level is not clear. To reveal identify the enzymes that contributeing to lignocellulose degraredauction and its degradation mechanisms, we evaluated transcriptomic how study theof T. versicolor transcriptome was changes during evaluated growthing on the poplar wood relative to growth on glucose medium. 853 genes were differentially expressed;, 360 genes were up-regulated on poplar wood, and 493 genes were down-regulated on poplar wood. Notably, most genes relative involved into lignin degradation were up-regulated, including eight lignin peroxidase (LiP) genes, and two manganese peroxidase (MnP) genes etc. Genes encoding cellulose and hemicelluloses degrading-enzymesation were mostly down-regulated, including six endo-β-1, 4-glucanase genes, three cellobiohydrolase I genes, and one cellobiohydrolase II gene, etc. MeanwhileAdditionally, expression of more significant expansion of P450s in T. versicolor genome, along with differences in carbohydrate- and lignin-degrading enzymes, could bewere correlated withto poplar wood degradation. Our results revealed transcriptomic characterizeation transcriptomic changes related toof lignocellulose degradation. Therefore, our results cwould be benuseful for the development ofefit T. versicolor as a tool to improve the efficiency of lignin degradation, and provide a theoretical foundation for a new paper pulp manufacturing processe 1,T.versicolor groewn on PDA medium. 2, T. versicolor growing on the a glucose carbon medium of glucose. 3, T. versicolor growing on poplar medium