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Annika Scheynius - One of the best experts on this subject based on the ideXlab platform.

  • extracellular vesicles released from the skin commensal yeast Malassezia sympodialis activate human primary keratinocytes
    Frontiers in Cellular and Infection Microbiology, 2020
    Co-Authors: Helen Vallhov, Catharina Johansson, Annika Scheynius, Rosanne E Veerman
    Abstract:

    Extracellular vesicles (EVs) released from fungi have been shown to participate in inter-organismal communication and in cross-kingdom modulation of host defence. Malassezia species are the dominant commensal fungal members of the human skin microbiota. We have previously found that Malassezia sympodialis releases EVs. These EVs, designated MalaEx, carry M. sympodialis allergens and induce a different inflammatory cytokine response in peripheral blood mononuclear cells from patients with atopic dermatitis compared to healthy controls. In this study we explored the host-microbe interaction between MalaEx and human keratinocytes with the hypothesis that MalaEx might be able to activate human keratinocytes to express the intercellular adhesion molecule-1 (ICAM-1, CD54) and to induce release of cytokines and/or chemokines. MalaEx were prepared from M. sympodialis (ATCC 42132) culture supernatants by a combination of centrifugation, filtration and serial ultracentrifugation. The MalaEx showed a size range of 70-580 nm with a mean of 154 nm using nanoparticle tracking analysis. MalaEx were found to induce a significant up-regulation of ICAM-1expression on primary human keratinocytes isolated from human ex vivo skin (p=0.026, n=3), compared to the unstimulated keratinocytes. In addition, the concentration of IL-1β was significantly increased in the MalaEx co-culture supernatants (p=0.027, n=3). Since, ICAM-1 is a counter ligand for the leukocyte integrins lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) induced expression on epithelial cells leads to attraction of immune competent cells. IL-1β is important for activation and recruitment of effector cells and a mediator in the inflammatory phase of healing processes in skin lesions. Thus, the capacity of MalaEx to activate keratinocytes with both an enhanced ICAM-1 expression and increased release of IL-1β indicate an important step in the cutaneous defence against M. sympodialis. How this modulation of host cells by a fungus is balanced between the commensal, pathogenic or beneficial states on the skin in the interplay with the host needs to be further elucidated.

  • Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin
    Scientific Reports, 2018
    Co-Authors: Henrik J. Johansson, Catharina Johansson, Tina Holm, Helen Vallhov, Anna Andersson, Ulf Gehrmann, Hans Blom, Marta Carroni, Janne Lehtiö, Annika Scheynius
    Abstract:

    Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M . sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M . sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.

  • curdlan induces selective mast cell degranulation without concomitant release of ltc4 il 6 or ccl2
    Immunobiology, 2017
    Co-Authors: Annika Scheynius, Gunnar Nilsson, Valeria C Barbosalorenzi, Simon Peyda, Carolina Lunderiusandersson
    Abstract:

    Abstract Mast cells are sentinel cells with a tissue-specific localization in the interface between the host and the external environment. Their quick and selective response upon encountering pathogens is part of the innate host response and typically initiates the following adaptive immune response. Among several pattern recognition receptors (PRRs) involved in the recognition of pathogens by mast cells, the C-type lectin receptor Dectin-1 has been associated with the recognition of fungi. Our previous studies have shown that mast cells are the predominant cell type expressing Dectin-1 in human skin, and they also recognize and respond to Malassezia sympodialis by producing cytokines connected to the innate host response and upregulating the expression of Dectin-1. In the present study, we investigated mast cell responses to Curdlan, a β-glucan that acts as an agonist for the fungi receptor Dectin-1, and found a unique response pattern with induced degranulation, but surprisingly without synthesis of Leukotriene C 4 , IL-6 or CCL2. Since mast cells are the predominant Dectin-1 expressing cell in the human skin, this study suggests that mast cell degranulation in response to fungi is an important part of the first line of defense against these pathogens.

  • identification of small rnas in extracellular vesicles from the commensal yeast Malassezia sympodialis
    Scientific Reports, 2017
    Co-Authors: Simon Rayner, Soren Bruhn, Helen Vallhov, Anna Andersson, Blake R Billmyre, Annika Scheynius
    Abstract:

    Malassezia is the dominant fungus in the human skin mycobiome and is associated with common skin disorders including atopic eczema (AE)/dermatitis. Recently, it was found that Malassezia sympodialis secretes nanosized exosome-like vesicles, designated MalaEx, that carry allergens and can induce inflammatory cytokine responses. Extracellular vesicles from different cell-types including fungi have been found to deliver functional RNAs to recipient cells. In this study we assessed the presence of small RNAs in MalaEx and addressed if the levels of these RNAs differ when M. sympodialis is cultured at normal human skin pH versus the elevated pH present on the skin of patients with AE. The total number and the protein concentration of the released MalaEx harvested after 48 h culture did not differ significantly between the two pH conditions nor did the size of the vesicles. From small RNA sequence data, we identified a set of reads with well-defined start and stop positions, in a length range of 16 to 22 nucleotides consistently present in the MalaEx. The levels of small RNAs were not significantly differentially expressed between the two different pH conditions indicating that they are not influenced by the elevated pH level observed on the AE skin.

  • Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes
    2016
    Co-Authors: Annika M. Sääf, Annika Scheynius, Maria Tengvall-linder, Howard Y. Chang, Adam S. Adler, Carl-fredrik Wahlgren, Maria Bradley
    Abstract:

    Background: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Methodology/Findings: We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusions/Significance: Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. W

Anna Andersson - One of the best experts on this subject based on the ideXlab platform.

  • Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin
    Scientific Reports, 2018
    Co-Authors: Henrik J. Johansson, Catharina Johansson, Tina Holm, Helen Vallhov, Anna Andersson, Ulf Gehrmann, Hans Blom, Marta Carroni, Janne Lehtiö, Annika Scheynius
    Abstract:

    Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M . sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M . sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.

  • proteogenomics produces comprehensive and highly accurate protein coding gene annotation in a complete genome assembly of Malassezia sympodialis
    Nucleic Acids Research, 2017
    Co-Authors: Par G Engstrom, Tina Holm, Anna Andersson, Blake R Billmyre, Christian Tellgrenroth, Charles D Baudo, John C Kennell, Markus S Schroder, Benjamin Sigurgeirsson, Guangxi Wu
    Abstract:

    Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotat ...

  • proteogenomics produces comprehensive and highly accurate protein coding gene annotation in a complete genome assembly of Malassezia sympodialis
    Nucleic Acids Research, 2017
    Co-Authors: Yafeng Zhu, Anna Andersson, Blake R Billmyre, Par G Engstrom, Christian Tellgrenroth, Charles D Baudo, John C Kennell, Sheng Sun, Markus S Schroder, Tina Holm
    Abstract:

    Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.

  • identification of small rnas in extracellular vesicles from the commensal yeast Malassezia sympodialis
    Scientific Reports, 2017
    Co-Authors: Simon Rayner, Soren Bruhn, Helen Vallhov, Anna Andersson, Blake R Billmyre, Annika Scheynius
    Abstract:

    Malassezia is the dominant fungus in the human skin mycobiome and is associated with common skin disorders including atopic eczema (AE)/dermatitis. Recently, it was found that Malassezia sympodialis secretes nanosized exosome-like vesicles, designated MalaEx, that carry allergens and can induce inflammatory cytokine responses. Extracellular vesicles from different cell-types including fungi have been found to deliver functional RNAs to recipient cells. In this study we assessed the presence of small RNAs in MalaEx and addressed if the levels of these RNAs differ when M. sympodialis is cultured at normal human skin pH versus the elevated pH present on the skin of patients with AE. The total number and the protein concentration of the released MalaEx harvested after 48 h culture did not differ significantly between the two pH conditions nor did the size of the vesicles. From small RNA sequence data, we identified a set of reads with well-defined start and stop positions, in a length range of 16 to 22 nucleotides consistently present in the MalaEx. The levels of small RNAs were not significantly differentially expressed between the two different pH conditions indicating that they are not influenced by the elevated pH level observed on the AE skin.

  • genomic insights into the atopic eczema associated skin commensal yeast Malassezia sympodialis
    Mbio, 2013
    Co-Authors: Anastasia Gioti, Anna Andersson, Bjorn Nystedt, Wenjun Li, Jun Xu, Anna F Averette, Karin Munch, Xuying Wang, Catharine Kappauf, Joanne M Kingsbury
    Abstract:

    ABSTRACT 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 globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci. IMPORTANCEMalassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.

Tina Holm - One of the best experts on this subject based on the ideXlab platform.

  • Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin
    Scientific Reports, 2018
    Co-Authors: Henrik J. Johansson, Catharina Johansson, Tina Holm, Helen Vallhov, Anna Andersson, Ulf Gehrmann, Hans Blom, Marta Carroni, Janne Lehtiö, Annika Scheynius
    Abstract:

    Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M . sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M . sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.

  • proteogenomics produces comprehensive and highly accurate protein coding gene annotation in a complete genome assembly of Malassezia sympodialis
    Nucleic Acids Research, 2017
    Co-Authors: Par G Engstrom, Tina Holm, Anna Andersson, Blake R Billmyre, Christian Tellgrenroth, Charles D Baudo, John C Kennell, Markus S Schroder, Benjamin Sigurgeirsson, Guangxi Wu
    Abstract:

    Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotat ...

  • proteogenomics produces comprehensive and highly accurate protein coding gene annotation in a complete genome assembly of Malassezia sympodialis
    Nucleic Acids Research, 2017
    Co-Authors: Yafeng Zhu, Anna Andersson, Blake R Billmyre, Par G Engstrom, Christian Tellgrenroth, Charles D Baudo, John C Kennell, Sheng Sun, Markus S Schroder, Tina Holm
    Abstract:

    Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.

  • cell penetrating peptides as antifungals towards Malassezia sympodialis
    Letters in Applied Microbiology, 2012
    Co-Authors: Tina Holm, Annika Scheynius, Julia Bruchmann, Ulo Langel
    Abstract:

    Aim:  To determine whether different antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) are able to inhibit the growth of the commensal yeast Malassezia sympodialis, which can act as a trigger factor in different skin disorders, such as atopic eczema (AE), seborrhoeic eczema (SE) and dandruff. Methods and results:  The antifungal activity of 21 different AMPs and CPPs was investigated by microdilution assay and plate counting to determine the number of colony forming units. Five CPPs and one AMP showed fungicidal activity at submicromolar concentrations. Importantly, no membrane damage on human keratinocytes was detected after peptide treatment. Conclusions:  Several CPPs, while being nontoxic to mammalian cells, possess growth inhibitory activity on the very stringent yeast M. sympodialis. Significance and impact of study:  Our findings that five CPPs and one AMP that are harmless towards mammalian cells act as antifungal agents against M. sympodialis opens up the possibility to use these in the treatment for AE, SE and dandruff. To our knowledge, this is the first time peptides have been identified as antifungal agents against M. sympodialis. Further studies to elucidate the mechanism are warranted.

Reto Crameri - One of the best experts on this subject based on the ideXlab platform.

  • Malassezia sympodialis thioredoxin specific t cells are highly cross reactive to human thioredoxin in atopic dermatitis
    The Journal of Allergy and Clinical Immunology, 2011
    Co-Authors: Hari Balaji, Annika Scheynius, Reto Crameri, Annice Heratizadeh, Katja Wichmann, Margarete Niebuhr, Thomas Werfel
    Abstract:

    BACKGROUND: IgE-mediated cross-reactivity between fungal antigens and human proteins has been described in patients with atopic dermatitis (AD), but it remains to be elucidated whether there is also cross-reactivity at the T-cell level. OBJECTIVE: We sought to explore cross-reactivity at the T-cell level between the fungal thioredoxin (Mala s 13) of the skin-colonizing yeast Malassezia sympodialis and its homologous human thioredoxin (hTrx). METHODS: T-cell lines (TCLs) were generated in the presence of rMala s 13 from the peripheral blood and from skin biopsy specimens of positive patch test reactions of patients with AD sensitized to Mala s 13 and hTrx. Patients with AD not sensitized to Malassezia species, healthy subjects, and patients with psoriasis served as control subjects. Mala s 13-specific T-cell clones (TCCs) were generated from TCLs. TCCs were characterized by antigen specificity, phenotype, and cytokine secretion pattern. Human keratinocytes were stimulated with IFN-γ, TNF-α, and IL-4, and the release of hTrx was determined by means of ELISA. RESULTS: Mala s 13-specific TCLs and TCCs from the blood and skin of patients with AD sensitized to Mala s 13 and hTrx were fully cross-reactive with hTrx. Mala s 13- and hTrx-specific TCCs could not be generated from control subjects. The majority of cross-reactive TCCs were CD4(+) and coexpressed cutaneous lymphocyte antigen. In addition to T(H)1 and T(H)2 TCCs, we could also identify TCCs secreting IL-17 and IL-22. After stimulation with IFN-γ and TNF-α, keratinocytes released substantial amounts of thioredoxin. CONCLUSION: In patients with AD sensitized to Malassezia species, cross-reactivity at the T-cell level to Mala s 13 and the homologous hTrx is detectable. hTrx autoreactive skin-homing T cells might be relevant for cutaneous inflammation in patients with AD.

  • crystal structure of the major Malassezia sympodialis allergen mala s 1 reveals a beta propeller fold a novel fold among allergens
    Journal of Molecular Biology, 2007
    Co-Authors: Monica Vilhelmsson, Annika Scheynius, Reto Crameri, Arezou Zargari, Omid Rasool, Adnane Achour, Martin B Hallberg
    Abstract:

    Abstract Atopic eczema (AE) is a chronic inflammatory disease in which genetic predisposition and environmental factors such as microorganisms contribute to the symptoms. The yeast Malassezia sympodialis , part of the normal human cutaneous flora, can act as an allergen eliciting specific IgE and T-cell reactivity in patients with AE. The major M. sympodialis allergen Mala s 1 is localized mainly in the yeast cell wall and exposed on the cell surface. Interestingly, Mala s 1 does not exhibit any significant sequence homology to known proteins. Here we present the crystal structure of Mala s 1 determined by single-wavelength anomalous dispersion techniques using selenomethionine-substituted Mala s 1. Mala s 1 folds into a 6-fold β-propeller, a novel fold among allergens. The putative active site of Mala s 1 overlaps structurally to putative active sites in potential homologues, Q4P4P8 and Tri 14, from the plant parasites Ustilago maydis and Gibberella zeae , respectively. This resemblance suggests that Mala s 1 and the parasite proteins may have similar functions. In addition, we show that Mala s 1 binds to the phosphoinositides (PI) PI(3)P, PI(4)P, and PI(5)P, lipids possibly playing a role in the localization of Mala s 1 to the cell surface. The crystal structure of Mala s 1 will provide insights into the role of this major allergen in the host–microbe interactions and induction of an allergic response in AE.

  • the Malassezia sympodialis allergen mala s 11 induces human dendritic cell maturation in contrast to its human homologue manganese superoxide dismutase
    International Archives of Allergy and Immunology, 2007
    Co-Authors: Monica Vilhelmsson, Catharina Johansson, Gunilla Jacobssonekman, Reto Crameri, Arezou Zargari, Annika Scheynius
    Abstract:

    Background: Recently, we identified a major Malassezia sympodialis allergen, Mala s 11, which displays a high degree of DNA sequence homology to human manganese s

  • cross reactivity and 1 4 a crystal structure of Malassezia sympodialis thioredoxin mala s 13 a member of a new pan allergen family
    Journal of Immunology, 2006
    Co-Authors: Andreas Limacher, Andreas G Glaser, Peter Schmidgrendelmeier, Christa Meier, Sabine Zeller, Leonardo Scapozza, Reto Crameri
    Abstract:

    We have identified thioredoxins (Trx) of Malassezia sympodialis, a yeast involved in the pathogenesis of atopic eczema, and of Aspergillus fumigatus, a fungus involved in pulmonary complications, as novel IgE-binding proteins. We show that these Trx, including the human enzyme, represent cross-reactive structures recognized by serum IgE from individuals sensitized to M. sympodialis Trx. Moreover, all three proteins were able to elicit immediate-type allergic skin reactions in sensitized individuals, indicating a humoral immune response based on molecular mimicry. To analyze structural elements involved in these reactions, the three-dimensional structure of M. sympodialis Trx (Mala s 13) has been determined at 1.4-A resolution by x-ray diffraction analysis. The structure was solved by molecular replacement and refined to a crystallographic R factor of 14.0% and a free R factor of 16.8% and shows the typical Trx fold. Mala s 13 shares 45% sequence identity with human Trx and superposition of the solved Mala s 13 structure with those of human Trx reveals a high similarity with a root mean square deviation of 1.11 A for all Calpha atoms. In a detailed analysis of the molecular surface in combination with sequence alignment, we identified conserved solvent-exposed amino acids scattered over the surface in both structures which cluster to patches, thus forming putative conformational B cell epitopes potentially involved in IgE-mediated cross- and autoreactivity.

  • sensitization to the yeast Malassezia sympodialis is specific for extrinsic and intrinsic atopic eczema
    Journal of Investigative Dermatology, 2006
    Co-Authors: Barbra Fischer Casagrande, Catharina Johansson, Annika Scheynius, Reto Crameri, Sabine Fluckiger, Maria Tengvall Linder, Peter Schmidgrendelmeier
    Abstract:

    The opportunistic yeast Malassezia sympodialis belongs to the normal cutaneous flora but can also cause IgE-mediated sensitization in patients suffering from atopic eczema (AE). We investigated 706 individuals by ImmunoCAPm70 and skin-prick tests with a crude M. sympodialis extract. In AE patients, we further performed skin prick tests, atopy patch tests, ELISA, and peripheral blood mononuclear cells proliferation assays with recombinant M. sympodialis allergens (rMala s 1 and 5–9). In 52/97 patients with AE-specific IgE against M. sympodialis was detectable. Almost no reactivity to M. sympodialis was seen in patients suffering from other allergic diseases (4/571) and no reactivity at all was seen in healthy controls (0/38). Skin tests showed variable recognition patterns against the different molecular structures with a predominant sensitization to rMala s 1, 5, 6, and 9, confirmed also by specific serum IgE to these allergens. Interestingly, IgE- and T-cell-mediated reactivity against M. sympodialis was also found in patients with the intrinsic form of AE. Thus, sensitization to M. sympodialis is specific for AE patients and occurs in both the extrinsic and intrinsic variant of eczema. Recombinant yeast allergens represent a useful tool to study molecular structures and differential sensitization patterns in the pathogenesis of AE.

Gustavo Giusiano - One of the best experts on this subject based on the ideXlab platform.

  • fungemia and interstitial lung compromise caused by Malassezia sympodialis in a pediatric patient
    Revista Iberoamericana De Micologia, 2015
    Co-Authors: Clarisa Aguirre, Maria De Los Angeles Sosa, Cristina Euliarte, J L Finquelievich, Gustavo Giusiano
    Abstract:

    A case of fungemia with interstitial lung compromise caused by Malassezia sympodialis is reported in an obese pediatric patient on long-term treatment with inhaled corticosteroids for asthma. The patient was hospitalized due to a post-surgical complication of appendicitis. The patient was treated with amphotericin B for 3 weeks, with good clinical evolution and subsequent negative cultures.

  • antifungal susceptibility of Malassezia furfur Malassezia sympodialis and Malassezia globosa to azole drugs and amphotericin b evaluated using a broth microdilution method
    Medical Mycology, 2014
    Co-Authors: Florencia Rojas, Maria De Los Angeles Sosa, Mariana S Fernandez, Maria Emilia Cattana, Susana B Cordoba, Gustavo Giusiano
    Abstract:

    We studied the in vitro activity of fluconazole (FCZ), ketoconazole (KTZ), miconazole (MCZ), voriconazole (VCZ), itraconazole (ITZ) and amphotericin B (AMB) against the three major pathogenicMalasseziaspecies,M. globosa,M. sympodialis,andM. furfur. Antifungal susceptibilities were determined using the broth microdilution method in accordance with Clinical and Laboratory Standards Institute reference document M27-A3. To support lipid-dependent yeast development, glucose, peptone, ox bile, malt extract, glycerol, and Tween supplements were added to Roswell Park Memorial Institute RPMI 1640 medium. The supplemented medium allowed good growth of all three species studied. The minimal inhibitory concentrations (MICs) were recorded after 72 h of incubation at 32 o C. The three species showed different susceptibility profiles for the drugs tested. Malassezia sympodialis was the most susceptible and M. furfur the least susceptible species. KTZ, ITZ, and VCZ were the most active drugs, showing low variability among isolates of the same species. FCZ, MCZ, and AMB showed high MICs and wide MIC ranges. Differences observed emphasize the need to accurately identify and evaluate antifungal susceptibility of Malassezia species. Further investigations and collaborative studies are essential for correlating in vitro results with clinical outcomes since the existing limited data do not allow definitive conclusions.

  • in vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species
    Mycoses, 2013
    Co-Authors: Alfonso Javier Carrillomunoz, María De Los Ángeles Sosa, Florencia Rojas, C Turtur, Gustavo Ortiz Diez, Carmen Martin Espada, Maria Jesus Paya, Gustavo Giusiano
    Abstract:

    The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen.