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Malassezia fungi predominantly reside on human skin and are associated with several skin diseases, such as seborrheic dermatitis. They have also been implicated in various other diseases, including inflammatory bowel disease (IBD). While Malassezia DNA has been detected in many fungal microbiome studies using fecal samples, no previous research had isolated live Malassezia strains from the gut or confirmed that live Malassezia cells reside within the gut environment. In this study, we successfully isolated live Malassezia globosa strains from the gut mucosal surface of ulcerative colitis patients and compared them to M. globosa skin isolates. Our results revealed significant differences in pathogenicity between the gut and skin isolates and suggest the important role of M. globosa in the gut and its involvement in IBD.

Microbial sequencing of samples obtained from multiple skin sites in healthy human adults shows that core-body and arm sites are dominated by fungal species of the genus Malassezia , whereas foot sites show high fungal diversity, and that skin topography is associated with differential compositions of bacterial and fungal communities. Skin microbes a mixed population As well as protecting against invasion by pathogens, our skin plays host to a varied population of microbes, some of which have important roles in human health and disease. The bacterial component of these communities is by now fairly well known, but our knowledge of the fungal members of the skin microbiota remains limited. Here Julia Segre and colleagues construct a map of the fungal species diversity at 14 different skin sites from 10 healthy adults, and compare this with the bacterial flora. They find that fungal richness varies across the body, and that bacterial and fungal communities are shaped by different factors. One finding with particular relevance to disease is that microbial communities around the feet that are commonly affected by fungal disease, such as athlete's foot, tend to be unstable. This instability may provide opportunities for harmful microbes to flourish. This finding highlights the need to develop new treatment strategies that specifically target microbial imbalances. Traditional culture-based methods have incompletely defined the microbial landscape of common recalcitrant human fungal skin diseases, including athlete’s foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms and provides a home for diverse commensal microbiota 1 . Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders 2 , 3 , 4 . However, microbial diversity is not limited to bacteria; microorganisms such as fungi also have major roles in microbial community stability, human health and disease 5 . Genomic methodologies to identify fungal species and communities have been limited compared with those that are available for bacteria 6 . Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes 7 . Here we sequenced and analysed fungal communities of 14 skin sites in 10 healthy adults. Eleven core-body and arm sites were dominated by fungi of the genus Malassezia , with only species-level classifications revealing fungal-community composition differences between sites. By contrast, three foot sites—plantar heel, toenail and toe web—showed high fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that physiologic attributes and topography of skin differentially shape these two microbial communities. These results provide a framework for future investigation of the contribution of interactions between pathogenic and commensal fungal and bacterial communities to the maintainenace of human health and to disease pathogenesis.

The ability to adapt to host pH has been previously associated with microbial virulence in several pathogenic fungal species. Here we demonstrate that a fungal-specific alkaline response pathway is conserved in the human skin commensal fungus Malassezia sympodialis ( Ms ). This pathway is characterized by the pH-dependent activation of the Rim101/PacC transcription factor that controls cell surface adaptations to changing environmental conditions. By disrupting genes encoding two predicted components of this pathway, we demonstrated that the Rim/Pal pathway is conserved in this fungal species as a facilitator of alkaline pH growth. Moreover, targeted gene mutation and comparative transcriptional analysis support the role of the Ms Rra1 protein as a cell surface pH sensor conserved within the basidiomycete fungi, a group including plant and human pathogens. Using an animal model of atopic dermatitis, we demonstrate the importance of Ms Rim/Pal signaling in this common inflammatory condition characterized by increased skin pH.

Background Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Results Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces , Malassezia , and Candida , with S. cerevisiae , M. restricta , and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae , M. restricta , and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Conclusions Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces , Malassezia , and Candida . Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual’s mycobiome is no more similar to itself over time than to another person’s. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.

Literature has suggested that Malassezia globosa is associated with breast tumors; however, this association has not been confirmed. Here, we found that M. globosa colonizes in breast fat pads leading to tumor growth. As a lipophilic yeast, the expression of sphingosine kinase 1 (Sphk1) was upregulated to promote tumor growth after M. globosa colonization. Moreover, the IL-17A/macrophages axis plays a key role in mechanisms involved in the M. globosa -induced breast cancer acceleration from the tumor immune microenvironment perspective.

Zoonotic yeast species have been implicated in disease development in both humans and cats. This study analyzed the yeast mycobiota present in feline facial hair and human nails and explored potential interspecies associations. A total of 118 biological specimens were examined, including 59 feline facial hair and 59 human nail samples. DNA extraction and DNA sequencing were performed to identify the specific yeast species. The most predominant yeast species in humans and cats were selected for antifungal susceptibility testing (itraconazole, ketoconazole, miconazole, and terbinafine). The findings unveiled diverse yeast species in cats and humans. Malassezia pachydermatis (45.8%) and Malassezia furfur (30.5%) were the most common yeast species in cats and humans, respectively. However, no significant correlation was detected between the yeast species identified in cats and their owners residing in the same household ( p  > 0.05). Miconazole exhibited the highest minimum inhibitory concentrations (MICs) against Malassezia pachydermatis and Malassezia furfur in both cat and human isolates, whereas terbinafine showed the lowest MICs against most Malassezia pachydermatis and Malassezia furfur in both cat and human isolates. Diverse yeast species in cat facial hair and human nails suggest possible cross-contamination among humans, pets, and environments.

Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex.

We describe a novel Malassezia species named Malassezia polysorbatinonusus, isolated from a Japanese patient with seborrheic dermatitis. The internal transcribed spacer (ITS) region of the isolate (LSEM 4845 T ) were only 94.7% identical to those of M. yamatoensis . A phylogenetic analysis of D1/D2 domain of 26S rDNA and β-TUB-encoding gene sequences also revealed that the novel isolate was distinct from the cluster formed by other Malassezia species. Notably, morphological characteristics and molecular analysis indicated that the novel species is most closely related to M. yamatoensis isolated from a Japanese patient with seborrheic dermatitis, although the two species exhibit different physiological characteristics. In contrast to M. yamatoensis , the novel isolate does not metabolize Tweens and can grow at 40 °C. These characteristics have historically distinguished animal Malassezia isolates from those isolated from humans. Therefore, we conclude the novel isolate constitutes a new species, which we designate M. polysorbatinonusus .

This study provides essential insights into interkingdom interactions within the human skin microbiome, highlighting how microbial metabolites influence fungal biology at the chromatin level. Specifically, we identify acetic acid (AcOH), secreted by Staphylococcus epidermidis , as a key regulator that induces significant chromatin remodeling and transcriptional changes in Malassezia restricta . By presenting the first three-dimensional genome architecture map of M. restricta , our findings uncover metabolite-specific chromatin dynamics that cannot be replicated by inorganic acid stress. Additionally, the conservation of this chromatin response in other Malassezia species suggests broader implications for understanding microbial adaptation mechanisms in the skin environment. This work underscores the critical role of bacterial metabolites as modulators of microbial interactions and provides new avenues for investigating microbial community balance and potential therapeutic strategies for skin health.

Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin's carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin.