Project description:Malassezia restricta, one of the predominant basidiomycetous yeasts present on human skin, is involved in scalp disorders. Here, we report the complete genome sequence of the lipophilic Malassezia restricta CBS 7877 strain, which will facilitate the study of the mechanisms underlying its commensal and pathogenic roles within the skin microbiome.
Project description:Chronic alcohol consumption is associated with intestinal fungal dysbiosis, yet we understand little about how alterations of intestinal fungi (mycobiota) contribute to the pathogenesis of alcohol-associated liver disease. By reanalyzing internal transcribed spacer 2 amplicon sequencing of fecal samples from a cohort of 66 patients with alcohol use disorder for presence (as opposed to relative abundance) of fungal species, we observed that the presence of Malassezia restricta was associated with increased markers of liver injury. M. restricta exacerbates ethanol-induced liver injury both in acute binge and chronic ethanol-feeding models in mice. Using bone marrow chimeric mice, we found that the disease exacerbating effect by M. restricta was mediated by C-type lectin domain family 4, member N on bone marrow-derived cells. M. restricta induces inflammatory cytokines and chemokines in Kupffer cells through C-type lectin domain family 4, member N signaling. Targeting fungal pathobionts might be a therapeutic strategy for alcohol-associated liver disease.
Project description:The draft genome sequence of Malassezia restricta KCTC 27527, a clinical isolate from a patient with dandruff, was previously reported. Using the PacBio Sequel platform, we completed and reannotated the genome of M. restricta KCTC 27527 for a better understanding of the genome of this fungus.
Project description:Dandruff is a common scalp disorder with multiple microbial and host-related factors contributing to its aetiology, including alterations in scalp sebum. Despite existing evidence that the yeast Malassezia restricta plays a key role in the onset of dandruff, the interplay of these factors is poorly understood. Recently, squalene monohydroperoxide and malondialdehyde were established as biomarkers of dandruff-afflicted scalp, highlighting the role of sebum lipoperoxidation in the triggering and maintenance of dandruff, although its mechanism of action is unknown. The current study provides evidence that M. restricta mediates sebum peroxidation, leading to production of squalene monohydroperoxide and malondialdehyde. Furthermore, in vitro data show that these lipoperoxidation products act on epidermal cells and alter the skin barrier. These results support the role of Malassezia restricta-induced lipoperoxides as triggers of dandruff, which suggests that blocking their production could be a novel anti-dandruff treatment approach.
Project description:Malassezia species are ubiquitous residents of human skin and are associated with several diseases such as seborrheic dermatitis, tinea versicolor, folliculitis, atopic dermatitis, and scalp conditions such as dandruff. Host-Malassezia interactions and mechanisms to evade local immune responses remain largely unknown. Malassezia restricta is one of the most predominant yeasts of the healthy human skin, its cell wall has been investigated in this paper. Polysaccharides in the M. restricta cell wall are almost exclusively alkali-insoluble, showing that they play an essential role in the organization and rigidity of the M. restricta cell wall. Fractionation of cell wall polymers and carbohydrate analyses showed that the polysaccharide core of the cell wall of M. restricta contained an average of 5% chitin, 20% chitosan, 5% ?-(1,3)-glucan, and 70% ?-(1,6)-glucan. In contrast to other yeasts, chitin and chitosan are relatively abundant, and ?-(1,3)-glucans constitute a minor cell wall component. The most abundant polymer is ?-(1,6)-glucans, which are large molecules composed of a linear ?-(1,6)-glucan chains with ?-(1,3)-glucosyl side chain with an average of 1 branch point every 3.8 glucose unit. Both ?-glucans are cross-linked, forming a huge alkali-insoluble complex with chitin and chitosan polymers. Data presented here show that M. restricta has a polysaccharide organization very different of all fungal species analyzed to date.
Project description:Malassezia restricta is an opportunistic fungal pathogen on human skin; it is associated with various skin diseases, including seborrheic dermatitis and dandruff, which are usually treated using ketoconazole. In this study, we clinically isolated ketoconazole-resistant M. restricta strains (KCTC 27529 and KCTC 27550) from patients with dandruff. To understand the mechanisms of ketoconazole resistance in the isolates, their genomes were sequenced and compared with the susceptible reference strain M. restricta KCTC 27527. Using comparative genome analysis, we identified tandem multiplications of the genomic loci containing ATM1 and ERG11 homologs in M. restricta KCTC 27529 and KCTC 27550, respectively. Additionally, we found that the copy number increase of ATM1 and ERG11 is reflected in the increased expression of these genes; moreover, we observed that overexpression of these homologs caused ketoconazole resistance in a genetically tractable fungal pathogen, Cryptococcus neoformans. In addition to tandem multiplications of the genomic region containing the ATM1 homolog, the PDR5 homolog, which encodes the drug efflux pump protein was upregulated in M. restricta KCTC 27529 compared to the reference strain. Biochemical analysis confirmed that drug efflux was highly activated in M. restricta KCTC 27529, implying that upregulation of the PDR5 homolog may also contribute to ketoconazole resistance in the strain. Overall, our results suggest that multiplication of the genomic loci encoding genes involved in ergosterol synthesis, mitochondrial iron metabolism, and oxidative stress response and overexpression of the drug efflux pumps are the mechanisms underlying ketoconazole resistance in M. restricta.
Project description:BackgroundThe lipophilic yeasts Malassezia spp. are normally resident on the surface of the human body, and often associated with various skin diseases. Of the 18 known Malassezia spp., Malassezia restricta is the most predominantly identified Malassezia sp. found on the human skin. Malassezia possesses a large number of genes encoding lipases to degrade human sebum triglycerides into fatty acids, which are required not only for their growth, but also trigger skin diseases. Previously, we have shown that MrLIP5 (MRET_0930), one of the 12 lipase genes in the genome of M. restricta, and is the most frequently expressed lipase gene in the scalp of patients with dandruff.ObjectiveIn this study, we aimed to analyze the activity, stability, and expression of MrLip5, with particular focus on pH.MethodsWe heterologously expressed MrLip5 in Escherichia coli, and purified and analyzed its activity and expression under different pH conditions.ResultsWe found that MrLip5 was most active and stable and highly expressed under alkaline conditions, which is similar to that of the diseased skin surface.ConclusionOur results suggest that the activity and expression of MrLip5 are pH-dependent, and that this lipase may play an essential role at the M. restricta-host interface during disease progression.