Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin

Dora E Corzo Leon; Annika Scheynius; Donna M MacCallum; Carol A Munro

doi:10.1093/femsyr/foad028

Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin

Dora E Corzo Leon^* (Corresponding Author), Annika Scheynius, Donna M MacCallum, Carol A Munro^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Malassezia are the dominant commensal yeast species of the human skin microbiota and are associated with inflammatory skin diseases, such as atopic eczema (AE). The Mala s 1 allergen of Malassezia sympodialis is a β-propeller protein, inducing both IgE and T-cell reactivity in AE patients. We demonstrate by immuno-electron microscopy that Mala s 1 is mainly located in the M. sympodialis yeast cell wall. An anti-Mala s 1 antibody did not inhibit M. sympodialis growth suggesting Mala s 1 may not be an antifungal target. In silico analysis of the predicted Mala s 1 protein sequence identified a motif indicative of a KELCH protein, a subgroup of β-propeller proteins. To test the hypothesis that antibodies against Mala s 1 cross-react with human skin (KELCH) proteins we examined the binding of the anti-Mala s 1 antibody to human skin explants and visualised binding in the epidermal skin layer. Putative human targets recognised by the anti-Mala s 1 antibody were identified by immunoblotting and proteomics. We propose that Mala s 1 is a KELCH-like β-propeller protein with similarity to human skin proteins. Mala s 1 recognition may trigger cross-reactive responses that contribute to skin diseases associated with M. sympodialis.

Original language	English
Number of pages	9
Journal	FEMS Yeast Research
Volume	23
Early online date	15 May 2023
DOIs	https://doi.org/10.1093/femsyr/foad028
Publication status	E-pub ahead of print - 15 May 2023

Bibliographical note

Open Access via the OUP Agreement

We thank Giuseppe Ianiri and Joe Heitman for their continuous support and many insightful discussions. Thanks to the Microscopy and Histology Facility at the Institute of Medical Sciences, University of Aberdeen, for sample processing and access to microscopes. Thanks to Dr. David Stead and the Aberdeen Proteomics Facility, University of Aberdeen for the proteomics analysis.

Funding
This project was funded by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). D.E.C.L., C.M,. and D.M. acknowledge funding from the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097 377/Z/11/Z. A.S. acknowledges, the Swedish Cancer and Allergy Fund.

Keywords

allergen
KELCH
Malassezia sympodialis
Mala s 1
commensal yeast
inflammatory skin disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/femsyr/foad028Licence: CC BY

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title = "Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin",

abstract = "Malassezia are the dominant commensal yeast species of the human skin microbiota and are associated with inflammatory skin diseases, such as atopic eczema (AE). The Mala s 1 allergen of Malassezia sympodialis is a β-propeller protein, inducing both IgE and T-cell reactivity in AE patients. We demonstrate by immuno-electron microscopy that Mala s 1 is mainly located in the M. sympodialis yeast cell wall. An anti-Mala s 1 antibody did not inhibit M. sympodialis growth suggesting Mala s 1 may not be an antifungal target. In silico analysis of the predicted Mala s 1 protein sequence identified a motif indicative of a KELCH protein, a subgroup of β-propeller proteins. To test the hypothesis that antibodies against Mala s 1 cross-react with human skin (KELCH) proteins we examined the binding of the anti-Mala s 1 antibody to human skin explants and visualised binding in the epidermal skin layer. Putative human targets recognised by the anti-Mala s 1 antibody were identified by immunoblotting and proteomics. We propose that Mala s 1 is a KELCH-like β-propeller protein with similarity to human skin proteins. Mala s 1 recognition may trigger cross-reactive responses that contribute to skin diseases associated with M. sympodialis.",

keywords = "allergen, KELCH, Malassezia sympodialis, Mala s 1, commensal yeast, inflammatory skin disease",

author = "{Corzo Leon}, {Dora E} and Annika Scheynius and MacCallum, {Donna M} and Munro, {Carol A}",

note = "Open Access via the OUP Agreement We thank Giuseppe Ianiri and Joe Heitman for their continuous support and many insightful discussions. Thanks to the Microscopy and Histology Facility at the Institute of Medical Sciences, University of Aberdeen, for sample processing and access to microscopes. Thanks to Dr. David Stead and the Aberdeen Proteomics Facility, University of Aberdeen for the proteomics analysis. Funding This project was funded by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). D.E.C.L., C.M,. and D.M. acknowledge funding from the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097 377/Z/11/Z. A.S. acknowledges, the Swedish Cancer and Allergy Fund.",

year = "2023",

month = may,

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doi = "10.1093/femsyr/foad028",

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T1 - Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin

AU - Corzo Leon, Dora E

AU - Scheynius, Annika

AU - MacCallum, Donna M

AU - Munro, Carol A

N1 - Open Access via the OUP Agreement We thank Giuseppe Ianiri and Joe Heitman for their continuous support and many insightful discussions. Thanks to the Microscopy and Histology Facility at the Institute of Medical Sciences, University of Aberdeen, for sample processing and access to microscopes. Thanks to Dr. David Stead and the Aberdeen Proteomics Facility, University of Aberdeen for the proteomics analysis. Funding This project was funded by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). D.E.C.L., C.M,. and D.M. acknowledge funding from the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097 377/Z/11/Z. A.S. acknowledges, the Swedish Cancer and Allergy Fund.

PY - 2023/5/15

Y1 - 2023/5/15

N2 - Malassezia are the dominant commensal yeast species of the human skin microbiota and are associated with inflammatory skin diseases, such as atopic eczema (AE). The Mala s 1 allergen of Malassezia sympodialis is a β-propeller protein, inducing both IgE and T-cell reactivity in AE patients. We demonstrate by immuno-electron microscopy that Mala s 1 is mainly located in the M. sympodialis yeast cell wall. An anti-Mala s 1 antibody did not inhibit M. sympodialis growth suggesting Mala s 1 may not be an antifungal target. In silico analysis of the predicted Mala s 1 protein sequence identified a motif indicative of a KELCH protein, a subgroup of β-propeller proteins. To test the hypothesis that antibodies against Mala s 1 cross-react with human skin (KELCH) proteins we examined the binding of the anti-Mala s 1 antibody to human skin explants and visualised binding in the epidermal skin layer. Putative human targets recognised by the anti-Mala s 1 antibody were identified by immunoblotting and proteomics. We propose that Mala s 1 is a KELCH-like β-propeller protein with similarity to human skin proteins. Mala s 1 recognition may trigger cross-reactive responses that contribute to skin diseases associated with M. sympodialis.

AB - Malassezia are the dominant commensal yeast species of the human skin microbiota and are associated with inflammatory skin diseases, such as atopic eczema (AE). The Mala s 1 allergen of Malassezia sympodialis is a β-propeller protein, inducing both IgE and T-cell reactivity in AE patients. We demonstrate by immuno-electron microscopy that Mala s 1 is mainly located in the M. sympodialis yeast cell wall. An anti-Mala s 1 antibody did not inhibit M. sympodialis growth suggesting Mala s 1 may not be an antifungal target. In silico analysis of the predicted Mala s 1 protein sequence identified a motif indicative of a KELCH protein, a subgroup of β-propeller proteins. To test the hypothesis that antibodies against Mala s 1 cross-react with human skin (KELCH) proteins we examined the binding of the anti-Mala s 1 antibody to human skin explants and visualised binding in the epidermal skin layer. Putative human targets recognised by the anti-Mala s 1 antibody were identified by immunoblotting and proteomics. We propose that Mala s 1 is a KELCH-like β-propeller protein with similarity to human skin proteins. Mala s 1 recognition may trigger cross-reactive responses that contribute to skin diseases associated with M. sympodialis.

KW - allergen

KW - KELCH

KW - Malassezia sympodialis

KW - Mala s 1

KW - commensal yeast

KW - inflammatory skin disease

U2 - 10.1093/femsyr/foad028

DO - 10.1093/femsyr/foad028

M3 - Article

C2 - 37188635

SN - 1567-1356

VL - 23

JO - FEMS Yeast Research

JF - FEMS Yeast Research

ER -

Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin

Abstract

Bibliographical note

Keywords

UN SDGs

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