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.

中文翻译：

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Malassezia sympodialis Mala s 1 过敏原是一种潜在的 KELCH 蛋白，可与人体皮肤发生交叉反应

马拉色菌是人类皮肤微生物群中主要的共生酵母菌种，与特应性湿疹 (AE) 等炎症性皮肤病有关。Malassezia sympodialis 的 Mala s 1 过敏原是一种 β-螺旋桨蛋白，可诱导 AE 患者的 IgE 和 T 细胞反应性。我们通过免疫电子显微镜证明 Mala s 1 主要位于 M. sympodialis 酵母细胞壁中。抗 Mala s 1 抗体不抑制 M. sympodialis 生长，表明 Mala s 1 可能不是抗真菌靶点。对预测的 Mala s 1 蛋白序列进行计算机分析，鉴定出指示 KELCH 蛋白（β-螺旋桨蛋白的一个亚组）的基序。为了检验抗 Mala s 1 抗体与人类皮肤 (KELCH) 蛋白发生交叉反应的假设，我们检查了抗 Mala s 1 抗体与人类皮肤外植体的结合，并可视化了表皮层中的结合。通过免疫印迹和蛋白质组学鉴定了抗 Mala s 1 抗体识别的假定人类靶标。我们认为 Mala s 1 是一种类似 KELCH 的 β-螺旋桨蛋白，与人类皮肤蛋白相似。Mala s 1 识别可能会引发交叉反应，从而导致与 M. sympodialis 相关的皮肤病。