School of Medicine, Medical Sciences & Nutrition University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden.
FEMS Yeast Res. 2023 Jan 4;23. doi: 10.1093/femsyr/foad028.
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 visualized binding in the epidermal skin layer. Putative human targets recognized 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.
马拉色菌是人类皮肤微生物群中的优势共生酵母物种，与炎症性皮肤病如特应性皮炎（AE）有关。糠秕马拉色菌的 Mala s 1 过敏原是一种β-三叶螺旋桨蛋白，在 AE 患者中诱导 IgE 和 T 细胞反应。我们通过免疫电子显微镜证明 Mala s 1 主要位于糠秕马拉色菌酵母细胞壁中。抗 Mala s 1 抗体不能抑制糠秕马拉色菌的生长，这表明 Mala s 1 可能不是抗真菌的靶标。对预测的 Mala s 1 蛋白序列的计算机分析确定了一个基序，表明它是 KELCH 蛋白的一个亚群，即β-三叶螺旋桨蛋白。为了测试抗 Mala s 1 抗体是否与人类皮肤（KELCH）蛋白发生交叉反应的假设，我们检查了抗 Mala s 1 抗体与人皮肤外植体的结合，并在表皮皮肤层中观察到结合。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。我们提出 Mala s 1 是一种具有与人皮肤蛋白相似性的 KELCH 样β-三叶螺旋桨蛋白。Mala s 1 的识别可能引发交叉反应性反应，从而导致与糠秕马拉色菌相关的皮肤疾病。
