•Cryptococcus neoformans is a complex of important human pathogens.•We provide evidence that at least seven species occur in the species complex.•The seven species are described, together with ...information on occurrence, epidemiology, virulence and host ranges.•MALDI-TOF MS can identify all seven species.
Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
spp. are lipid-dependent yeasts, inhabiting the skin and mucosa of humans and animals. They are involved in a variety of skin disorders in humans and animals and may cause bloodstream infections in ...severely immunocompromised patients. Despite a tremendous increase in scientific knowledge of these yeasts during the last two decades, the epidemiology of
spp. related to fungemia remains largely underestimated most likely due to the difficulty in the isolation of these yeasts species due to their lipid-dependence. This review summarizes and discusses the most recent literature on
spp. infection and fungemia, its occurrence, pathogenicity mechanisms, diagnostic methods,
susceptibility testing and therapeutic approaches.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recognition of fungal pathogens by C-type lectin receptor (CLR) dectin-1 on human dendritic cells is essential for triggering protective antifungal TH1 and TH17 immune responses. We show that ...Fonsecaea monophora, a causative agent of chromoblastomycosis, a chronic fungal skin infection, evades these antifungal responses by engaging CLR mincle and suppressing IL-12, which drives TH1 differentiation. Dectin-1 triggering by F. monophora activates transcription factor IRF1, which is crucial for IL12A transcription via nucleosome remodeling. However, simultaneous F. monophora binding to mincle induces an E3 ubiquitin ligase Mdm2-dependent degradation pathway, via Syk-CARD9-mediated PKB signaling, that leads to loss of nuclear IRF1 activity, hence blocking IL12A transcription. The absence of IL-12 leads to impaired TH1 responses and promotes TH2 polarization. Notably, mincle is similarly exploited by other chromoblastomycosis-associated fungi to redirect TH responses. Thus, mincle is a fungal receptor that can suppress antifungal immunity and, as such, is a potential therapeutic target.
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•Fungal engagement of Mincle opposes dectin-1-induced antifungal TH1 immune responses•Mincle activates PKB and E3 ligase Mdm2 to target nuclear IRF1 for degradation•IRF1 is crucial to IL12A transcription via nucleosome remodeling•Reduced levels of IL-12, a TH1-polarizing cytokine, decreases protective TH1 responses
Fungal recognition by C-type lectin receptor (CLR) dectin-1 triggers protective TH1 and TH17 immunity. Wevers et al. show that causative agents of chromoblastomycosis, such as Fonsecaea monophora, exploit signaling via CLR mincle to reduce expression of the TH1-polarizing cytokine IL-12 and thus suppress antifungal TH1 immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Irritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity is thought to be responsible for pain complaints ...in a subset of patients. In an IBS-like animal model, visceral hypersensitivity was triggered by intestinal fungi, and lower mycobiota α-diversity in IBS patients was accompanied by a shift toward increased presence of Candida albicans and Saccharomyces cerevisiae. Yet, this shift was observed in hypersensitive as well as normosensitive patients and diversity did not differ between IBS subgroups. The latter suggests that, when a patient changes from hyper- to normosensitivity, the relevance of intestinal fungi is not necessarily reflected in compositional mycobiota changes. We now confirmed this notion by performing ITS1 sequencing on an existing longitudinal set of fecal samples. Since ITS1 methodology does not recognize variations within species, we next focused on heterogeneity within cultured healthy volunteer and IBS-derived C. albicans strains. We observed inter- and intra-individual genomic variation and partial clustering of strains from hypersensitive patients. Phenotyping showed differences related to growth, yeast-to-hyphae morphogenesis and gene expression, specifically of the gene encoding fungal toxin candidalysin. Our investigations emphasize the need for strain-specific cause-and-effect studies within the realm of IBS research.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
S1.3 Malassezia: genetics, genomics, and biology, September 21, 2022, 11:00 AM - 12:30 PM
The Basidiomycetous yeast Malassezia is the most abundant fungal genus on healthy human skin but ...may also cause various skin disorders such as seborrheic dermatitis, dandruff, and pityriasis versicolor. In recent years, Malassezia has increasingly been implicated in health and disease beyond the skin: as an underestimated cause of Malassezia bloodstream infections (BSIs) in immunocompromised patients and neonates, associated with Crohn's disease, promoting pancreatic oncogenesis, and exacerbating cystic fibrosis. Malassezia furfur is the number one Malassezia BSI cause and is also implicated in many skin disorders. With these new discoveries of Malassezia’s impact on human health, the need for a better understanding of its evolution and pathobiology also became more pressing. Hybridization has been suggested as a biological mechanism of adaptation to new hosts, and may lead to increased pathogenicity. Many examples of major hybrid yeast pathogens exist, such as Candida albicans, C. orthopsilosis, C. metapsilosis, and multiple examples in the Cryptococcus gattii/Cryptococcus neoformans species complex. Here the multiple hybridization events of the Malassezia furfur species complex will be discussed. Two distinct hybridization events occurred between the same parental lineages, and these parental strains were originally also hybrids. The identification of a pseudobipolar mating system and the analysis of the mating-type loci provide evidence that sexual liaisons of mating compatible cells from these parental lineages led to a diploid/aneuploid state in the hybrid lineages. Sequence similarity percentages suggest that both parental lineages in fact are two different species. The genetic diversity of ca 300 strains belonging to this species complex is evaluated in relationship to host background and phenotype.
Mitogenomes are essential due to their contribution to cell respiration. Recently they have also been implicated in fungal pathogenicity mechanisms. Members of the basidiomycetous yeast genus ...Malassezia are an important fungal component of the human skin microbiome, linked to various skin diseases, bloodstream infections, and they are increasingly implicated in gut diseases and certain cancers. In this study, the comparative analysis of Malassezia mitogenomes contributed to phylogenetic tree construction for all species. The mitogenomes presented significant size and gene order diversity which correlates to their phylogeny. Most importantly, they showed the inclusion of large inverted repeats (LIRs) and G-quadruplex (G4) DNA elements, rendering Malassezia mitogenomes a valuable test case for elucidating the evolutionary mechanisms responsible for this genome diversity. Both LIRs and G4s coexist and convergently evolved to provide genome stability through recombination. This mechanism is common in chloroplasts but, hitherto, rarely found in mitogenomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The
genus comprises lipid-dependent yeasts that have long been associated with common skin diseases, and have recently been linked with Crohn's disease and certain cancers. Understanding
...susceptibility to diverse antimicrobial agents is crucial for identifying effective antifungal therapies. Here, we tested the efficacy of isavuconazole, itraconazole, terbinafine, and artemisinin against three
species:
,
and
. Using broth microdilution, we found antifungal properties for the two previously unstudied antimicrobials: isavuconazole and artemisinin. Overall, all
species were particularly susceptible to itraconazole, with a MIC range from 0.007 to 0.110 μg/mL.
The
genus is known to be involved in a variety of skin conditions and has recently been associated with diseases such as Crohn's disease, pancreatic ductal carcinoma, and breast cancer. This work was completed to assess susceptibility to a variety of antimicrobial drugs on three
species, in particular
, which is an abundant
species both on human skin and internal organs and has been implicated in Crohn's disease. We tested two previously unstudied drugs and developed a new testing method to overcome current limitations for measuring growth inhibition of slow-growing
strains.
species are important fungal skin commensals and are part of the normal microbiota of humans and other animals. However, under certain circumstances these fungi can also display a pathogenic ...behavior. For example,
is a common commensal of human skin and yet is often responsible for skin disorders but also systemic infections. Comparative genomics analysis of
revealed that some isolates have a hybrid origin, similar to several other recently described hybrid fungal pathogens. Because hybrid species exhibit genomic plasticity that can impact phenotypes, we sought to elucidate the genomic evolution and phenotypic characteristics of
hybrids in comparison to their parental lineages. To this end, we performed a comparative genomics analysis between hybrid strains and their presumptive parental lineages and assessed phenotypic characteristics. Our results provide evidence that at least two distinct hybridization events occurred between the same parental lineages and that the parental strains may have originally been hybrids themselves. Analysis of the mating-type locus reveals that
has a pseudobipolar mating system and provides evidence that after sexual liaisons of mating compatible cells, hybridization involved cell-cell fusion leading to a diploid/aneuploid state. This study provides new insights into the evolutionary trajectory of
and contributes with valuable genomic resources for future pathogenicity studies.
is a common commensal member of human/animal microbiota that is also associated with several pathogenic states. Recent studies report involvement of
species in Crohn's disease, a type of inflammatory bowel disease, pancreatic cancer progression, and exacerbation of cystic fibrosis. A recent genomics analysis of
.
revealed the existence of hybrid isolates and identified their putative parental lineages. In this study, we explored the genomic and phenotypic features of these hybrids in comparison to their putative parental lineages. Our results revealed the existence of a pseudobipolar mating system in this species and showed evidence for the occurrence of multiple hybridization events in the evolutionary trajectory of
. These findings significantly advance our understanding of the evolution of this commensal microbe and are relevant for future studies exploring the role of hybridization in the adaptation to new niches or environments, including the emergence of pathogenicity.
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