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Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globo...
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Citations
... We annotated the core genes for two central sexuality-related features in the life cycle of the fungi: mating and meiosis. This includes both mating loci (PR and HD), as well as 20 core meiosis genes described for Ustilaginomycotina [19][20][21]. We tested the conservation of the annotated genes in silico and assessed potential functionality. ...
... However, mating genes have previously been detected in representatives of the putatively asexual human pathogenic species of Malassezia (Malasseziales) [19], which could imply that mating related genes are maintained despite the potential loss of sexual reproduction. Assuming that members of Pseudozyma are able to mate, we showed that they would be self-sterile (heterothallic), containing either one or two pheromones compatible with other mating-types but not their own receptor, as all other known members of Ustilaginaceae [41]. ...
... We were able to detect and annotate all core meiosis gene as defined for Ustilago maydis [19] in the genomes from Pseudozyma strains (Fig. 2, Supplementary Table 1) and showed that most of them displayed no relaxed selection in the examined genomes (Table 2). In addition, all core meiotic genes have shown syntenic locus organization in closely related species throughout all meiotic functions ( Supplementary Fig. 3) and maintained functional protein domains ( Supplementary Tables 1 and 2). ...
Background
The Ustilaginales comprise hundreds of plant-parasitic fungi with a characteristic life cycle that directly links sexual reproduction and parasitism: One of the two mating-type loci codes for a transcription factor that not only facilitates mating, but also initiates the infection process. However, several species within the Ustilaginales have no described parasitic stage and were historically assigned to the genus Pseudozyma. Molecular studies have shown that the group is polyphyletic, with members being scattered in various lineages of the Ustilaginales. Together with recent findings of conserved fungal effectors in these non-parasitic species, this raises the question if parasitism has been lost recently and in multiple independent events or if there are hitherto undescribed parasitic stages of these fungi.
Results
In this study, we sequenced genomes of five Pseudozyma species together with six parasitic species from the Ustilaginales to compare their genomic capability to perform two central functions in sexual reproduction: mating and meiosis. While the loss of sexual capability is assumed in certain lineages and asexual species are common in Asco- and Basidiomycota, we were able to successfully annotate potentially functional mating and meiosis genes that are conserved throughout the whole group.
Conclusion
Our data suggest that at least the key functions of a sexual lifestyle are maintained in the analyzed genomes, challenging the current understanding of the so-called asexual species with respect to their evolution and ecological role.
... The MAT a and b loci of the M. furfur haploid strains analyzed are ;590 kb apart (see Table S2A), suggesting a pseudobipolar configuration. A representative comparison of the MAT loci of CBS14139 (MAT a1b1) and CBS7982 (MAT a2b2), as model strains, is shown in Fig. 4. The M. furfur MAT structure reflects that of the MAT locus of M. yamatoensis (16,20) and differs from the M. globosa and M. sympodialis MAT loci, for which MAT a and MAT b are ;167 and ;140 kb apart, respectively (20,22). This is consistent with a whole-genome based clustering that groups M. furfur and M. yamatoensis in a separate phylogenetic cluster within the Malassezia genus (16). ...
... The MAT a and b loci of the M. furfur haploid strains analyzed are ;590 kb apart (see Table S2A), suggesting a pseudobipolar configuration. A representative comparison of the MAT loci of CBS14139 (MAT a1b1) and CBS7982 (MAT a2b2), as model strains, is shown in Fig. 4. The M. furfur MAT structure reflects that of the MAT locus of M. yamatoensis (16,20) and differs from the M. globosa and M. sympodialis MAT loci, for which MAT a and MAT b are ;167 and ;140 kb apart, respectively (20,22). This is consistent with a whole-genome based clustering that groups M. furfur and M. yamatoensis in a separate phylogenetic cluster within the Malassezia genus (16). ...
... This is consistent with a whole-genome based clustering that groups M. furfur and M. yamatoensis in a separate phylogenetic cluster within the Malassezia genus (16). In all M. furfur haploid strains analyzed, the two MAT a locus genes are divergently oriented, corroborating previous findings for other Malassezia species (16,20,22). Moreover, a comparison between the MAT a1 and a2 loci revealed that the Mfa and Pra genes have an opposite arrangement albeit being located in highly syntenic flanking regions (Fig. 4). ...
Malassezia furfur is a common commensal member of human/animal microbiota that is also associated with several pathogenic states. Recent studies report involvement of Malassezia species in Crohn’s disease, a type of inflammatory bowel disease, pancreatic cancer progression, and exacerbation of cystic fibrosis.
... Detailed knowledge on Malassezia mt genomes and genes is scarce. A study focusing on M. sympodialis, explored the mt genome of this species (Gioti et al. 2013) revealing a typical mt genome of 38 622 bp containing 15 protein-coding genes, two rRNA genes and 25 tRNAs (Gioti et al. 2013). Another study on comparative genomics of various Malassezia species compared general phylogenetic topologies between nuclear and mt genes and concluded that both trees corresponded well at an inter-species level. ...
... Detailed knowledge on Malassezia mt genomes and genes is scarce. A study focusing on M. sympodialis, explored the mt genome of this species (Gioti et al. 2013) revealing a typical mt genome of 38 622 bp containing 15 protein-coding genes, two rRNA genes and 25 tRNAs (Gioti et al. 2013). Another study on comparative genomics of various Malassezia species compared general phylogenetic topologies between nuclear and mt genes and concluded that both trees corresponded well at an inter-species level. ...
... 8000 bp with three included genes (atp9, trnL and trnR), interrupted by a ca 550 bp intra-IR fragment, found in two orientations among different strains. Similarly, an inverted repeat region was previously also identified for M. sympodialis, with a size of 5900 bp (Gioti et al. 2013;Zhu et al. 2017). These large IRs are common in fungal mt genomes and have been described for a plethora of fungal genera, including the ascomycetous yeast genus Candida, significantly fluctuating in length from 109 bp in Candida salmanticensis to 14 379 bp in Candida maltosa, with varying gene content, and having a substantial impact on mt genome size (Valach et al. 2011). ...
Malassezia furfur is a yeast species belonging to Malasseziomycetes, Ustilaginomycotina, Basidiomycota that is found on healthy warm-blooded animal skin, but also involved in various skin disorders like seborrheic dermatitis/dandruff and pityriasis versicolor. Moreover, Malassezia are associated with bloodstream infections, Crohn's disease, and pancreatic carcinoma. Recent advances in Malassezia genomics and genetics have focused on the nuclear genome. In this work we present the M. furfur mitochondrial genetic heterogenicity with full analysis of 14 novel and six available M. furfur mt genomes. The mitogenome analysis reveals a mt gene content typical for fungi, including identification of variable mt regions suitable for intra-species discrimination. Three of them, namely the trnK-atp6 and cox3-nad3 intergenic regions and intron 2 of the cob gene, were selected for primer design to identify strain differences. M. furfur strains belonging to known genetic variable clusters, based on AFLP and nuclear loci, were assessed for their mt variation using PCR amplification and sequencing. The results suggest that these mt regions are excellent molecular markers for the typing of M. furfur strains and may provide added value to nuclear regions when assessing evolutionary relationships at the intraspecies level.
... After protein BLAST search of the MGL_3153 protein, more than 50% similarity with the GpiPs of several Malassezia species was observed. GpiPs have been identified in different fungi, and various roles including adhesion, biofilm formation, diverse enzymatic properties, virulence, and cell wall biosynthesis pathway have been mentioned for them [11, 13, 14, 38,39]. Studies on the role of GpiPs in Fusarium graminearum have shown that these proteins are essential to the growth, ramification, adhesion, virulence, and shaping of macroconidia [40]. ...
Glycosylphosphatidylinositols (GPI) -anchored proteins (GpiPs) are related to the cell wall biogenesis, adhesion, interactions, protease activity, mating, etc. These proteins have been identified in many organisms, including fungi such as Neurospora crassa, Candida albicans, Saccharomyces cerevisiae, and Fusarium graminearum. MGL-3153 gene of Malassezia. globosa (M. globosa) encodes a protein which is homologous of the M. restricta, M. sympodialis, M. Pachydermatis, and U. maydis GpiPs. Real-time PCR assay showed that the expression of MGL_3153 gene was significantly up-regulated among M. globosa isolated from patients with pityriasis versicolor (PV) compared to a healthy individual, suggesting the contribution of this gene in the virulence of M. globosa. Accordingly, the sequence of this protein was analyzed by bioinformatics tools to evaluate the structure of that. The conservation analysis of MGL-3153 protein showed that the C-terminal region of this protein, which is responsible for GPI-anchor ligation, was highly conserved during evolution while the N-terminal region just conserved in Malassezia species. Moreover, the predicted tertiary structure of this protein by homology modeling showed that this protein almost has alpha helix structure, and represented a stable structure during 100 nanosecond of Molecular Dynamics simulation. Our results revealed that this protein potentially belongs to GPI-anchored proteins, and may contribute to the virulence of M. globosa which warrants further investigations in this area.
... Interestingly, Johansson and coworkers performed cryo-EM analysis of Malassezia sympodialis EVs, demonstrating no evident decoration on their surfaces (Johansson et al., 2018). Comparative genomic analysis suggested that this lipophilic pathogenic yeast, living on the skin (Theelen et al., 2018), lacks the N-glycosylation pathway and possesses only a very small number of GPI-anchor proteins (Gioti et al., 2013). Accordingly, M. sympodialis cells lack the extensive mannan outer fibrillar layer, which can be easily observed at the surface of the cell wall of most yeasts including S. cerevisiae or C. albicans (Gioti et al., 2013;Muszewska et al., 2017). ...
... Comparative genomic analysis suggested that this lipophilic pathogenic yeast, living on the skin (Theelen et al., 2018), lacks the N-glycosylation pathway and possesses only a very small number of GPI-anchor proteins (Gioti et al., 2013). Accordingly, M. sympodialis cells lack the extensive mannan outer fibrillar layer, which can be easily observed at the surface of the cell wall of most yeasts including S. cerevisiae or C. albicans (Gioti et al., 2013;Muszewska et al., 2017). Therefore, it is very tempting to hypothesize that this absence of mannans in M. sympodialis could explain the absence of EV decoration, supporting the idea that EV decoration in Cryptococcus species is mannoprotein-based. ...
Whereas extracellular vesicle (EV) research has become commonplace in different biomedical fields, this field of research is still in its infancy in mycology. Here we provide a robust set of data regarding the structural and compositional aspects of EVs isolated from the fungal pathogenic species Cryptococcus neoformans, C. deneoformans and C. deuterogattii. Using cutting‐edge methodological approaches including cryogenic electron microscopy and cryogenic electron tomography, proteomics, and flow cytometry, we revisited cryptococcal EV features and suggest a new EV structural model, in which the vesicular lipid bilayer is covered by mannoprotein‐based fibrillar decoration, bearing the capsule polysaccharide as its outer layer. About 10% of the EV population is devoid of fibrillar decoration, adding another aspect to EV diversity. By analysing EV protein cargo from the three species, we characterized the typical Cryptococcus EV proteome. It contains several membrane‐bound protein families, including some Tsh proteins bearing a SUR7/PalI motif. The presence of known protective antigens on the surface of Cryptococcus EVs, resembling the morphology of encapsulated virus structures, suggested their potential as a vaccine. Indeed, mice immunized with EVs obtained from an acapsular C. neoformans mutant strain rendered a strong antibody response in mice and significantly prolonged their survival upon C. neoformans infection.
... The presence of mannoproteins in EV preparations was also reported in other fungal pathogens (Dawson et al. 2020;Karkowska-Kuleta et al. 2020). However, in M. sympodialis, which is largely devoid of GPI-anchor proteins and many other fungal typical mannoproteins (Gioti et al. 2013), EVs exhibit no evidence of decoration on their surface (Johansson et al. 2018). This highlights significant structural diversity in fungal EVs. ...
Extracellular vesicles (EVs) are lipidic nanosized particles that deliver a highly complex molecular cargo between cells and organisms and may serve numerous functions in intercellular communication, thereby influencing the evolution of microbial communities. Their roles in infectious diseases have been studied for a long time, comprising viral, bacterial, parasitic, and to a less extent, fungal infections. Over the last few years, fungal EVs have become an increasingly active research field. Nevertheless, the understanding of EV functions during fungal infections poses challenging points, comprising the genetics regulating EV release, the EV structural and compositional complexity, the heterogeneity of the EV populations, and their impact on host-pathogen interactions. This review explores the state-of-the-art investigations on fungal EVs and how this fast-evolving field can impact the development of new tools to fight fungal infections.
... We sampled sixteen representative genomes in Ustilaginomycotina to examine how the arrangement of the MAT loci is conserved in this subphylum ( [13,[75][76][77][78][79][80][81]; Figure 3). First, we found that most studied species have the tetrapolar mating system, except Testicularia cyperi and Malassezia globosa, which are bipolar, and Exobasidium vaccinii, which is strictly bipolar (i.e., genes in the MAT b locus are located right next to genes in the MAT a locus). ...
... Sixteen Ustilaginomycotina genomes were used in these analyses: Ustilago maydis [75], Sporisorium reilianum [76], Pseudozyma hubeiensis [77], Pseudozyma antarctica [78], Malassezia globosa [79], Malassezia sympodialis [80], Tilletiaria anomala [81], Exobasidium vaccinii [158], Acaromyces ingoldii, Ceraceosorus guamensis, Jaminaea rosea, Meira miltonrushii, Pseudomicrostroma glucosiphilum, Testicularia cyperi, Tilletiopsis washingtonensis and Violaceomyces palustris [13]. Genes in MAT loci were determined by blasting reference protein sequences from U. maydis genes against other species. ...
The corn smut fungus Ustilago maydis serves as a model species for studying fungal dimorphism and its role in phytopathogenic development. The pathogen has two growth phases: a saprobic yeast phase and a pathogenic filamentous phase. Dimorphic transition of U. maydis involves complex processes of signal perception, mating, and cellular reprogramming. Recent advances in improvement of reference genomes, high-throughput sequencing and molecular genetics studies have been expanding research in this field. However, the biology of other non-model species is frequently overlooked. This leads to uncertainty regarding how much of what is known in U. maydis is applicable to other dimorphic fungi. In this review, we will discuss dimorphic fungi in the aspects of physiology, reproductive biology, genomics, and molecular genetics. We also perform comparative analyses between U. maydis and other fungi in Ustilaginomycotina, the subphylum to which U. maydis belongs. We find that lipid/hydrophobicity is a potential common cue for dimorphic transition in plant-associated dimorphic fungi. However, genomic profiles alone are not adequate to explain dimorphism across different fungi.
... One of the most notable physiological characteristics of Malassezia spp. is their lipid-dependency. Recent genome sequencing analysis has revealed that the lipophilic nature of Malassezia spp. is caused by the lack of a fatty acid synthase gene [11][12][13][14][15] . This physiological characteristic might be compensated for by secretion of lipolytic enzymes, including lipases, which are hydrolases that act on carboxylic ester bonds, resulting in the production of free fatty acids 16 . ...
... An antiserum against M. restricta MrLip5 was generated by a custom antibody production service using the synthesized peptide representing the protein ( 477 KGDISPGEGGD HTKES 492 , Young In Frontier Inc., Seoul, Korea). Briefly, for the first immunization, an emulsion produced by mixing 11,13,39,40 . Hash marks indicate the conserved lipase motif (G-X-S-X-G). ...
Background:
The 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.
Objective:
In this study, we aimed to analyze the activity, stability, and expression of MrLip5, with particular focus on pH.
Methods:
We heterologously expressed MrLip5 in Escherichia coli, and purified and analyzed its activity and expression under different pH conditions.
Results:
We found that MrLip5 was most active and stable and highly expressed under alkaline conditions, which is similar to that of the diseased skin surface.
Conclusion:
Our 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.
... Tansley review New Phytologist mating types among its progeny, instead of four as occurs with unlinked mating-type loci; a given gamete is therefore compatible with half of other gametes instead of one quarter of them. The linkage of the two mating-type loci thus is beneficial under selfing, and has occurred repeatedly in several basidiomycete genera, such as the Microbotryum anther-smuts (Branco et al., 2017), the Cryptococcus human pathogen (Fraser & Heitman, 2005), the Malassezia human pathogens (Xu et al., 2007;Gioti et al., 2013), and the Sporisorium and Ustilago cereal smuts (Bakkeren & Kronstad, 1994;Que et al., 2014;Taniguti et al., 2015;Rabe et al., 2016;Liang et al., 2019). The region of suppressed recombination linking HD and PR loci can span from c. 100 kb and 20 genes in C. neoformans to 600 genes and megabases of DNA in Microbotryum fungi (Fraser & Heitman, 2005;Branco et al., 2017), trapping in-between many genes with no functions in mating. ...
Genomic regions determining sexual compatibility often display recombination suppression, as occurs in sex chromosomes, plant self-incompatibility loci and fungal mating-type loci. Regions lacking recombination can extend beyond the genes determining sexes or mating types, by several successive steps of recombination suppression. Here we review the evidence for recombination suppression around mating-type loci in fungi, sometimes encompassing vast regions of the mating-type chromosomes. The suppression of recombination at mating-type loci in fungi has long been recognized and maintains the multi-allelic combinations required for correct compatibility determination. We review more recent evidence for expansions of recombination suppression beyond mating-type genes in fungi ("evolutionary strata"), which have been little studied and may be more pervasive than commonly thought. We discuss testable hypotheses for the ultimate (evolutionary) and proximate (mechanistic) causes for such expansions of recombination suppression, including i) antagonistic selection, ii) association of additional functions to mating-type, such as uniparental mitochondria inheritance, iii) accumulation in the margin of non-recombining regions of various factors, including deleterious mutations or transposable elements due to relaxed selection, or neutral rearrangements due to genetic drift. The study of recombination suppression in fungi could thus contribute to our understanding of recombination suppression expansion across a broader range of organisms.
... Advances in sequencing technology have enabled detailed characterization of the genome sequences of skin-residing microbes isolated through both culture-dependent and culture-independent methods (Grice, 2015;Byrd et al., 2017). Functional annotations of the Malassezia genome have revealed the presence of many genes encoding for hydrolytic enzymes-namely proteases, esterases (including lipases and phospholipases) and glucosyl hydrolases (Xu et al., 2007;Gioti et al., 2013;Park et al., 2017;Zhu et al., 2017). This is especially relevant for the skin environment which is nutrient-poor and enriched with lipids and proteins (Chen et al., 2018). ...
Malassezia is the most abundant eukaryotic microbial genus on human skin. Similar to many human-residing fungi, Malassezia has high metabolic potential and secretes a plethora of hydrolytic enzymes that can potentially modify and structure the external skin environment. Here we show that the dominant secreted Malassezia protease isolated from cultured Malassezia furfur is an aspartyl protease that is secreted and active at all phases of culture growth. We observed that this protease, herein named as MfSAP1 (M. furfur secreted aspartyl protease 1) has a broader substrate cleavage profile and higher catalytic efficiency than the previously reported protease homolog in Malassezia globosa. We demonstrate that MfSAP1 is capable of degrading a wide range of human skin associated extracellular matrix (ECM) proteins and ECM isolated directly from keratinocytes and fibroblasts. Using a 3-D wound model with primary keratinocytes grown on human de-epidermized dermis, we show that MfSAP1 protease can potentially interfere with wound re-epithelization in an acute wound model. Taken together, our work demonstrates that Malassezia proteases have host-associated substrates and play important roles in cutaneous wound healing.
