Shanghai Tenth People's Hospital, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, P.R. China.
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P.R. China.
Sci Rep. 2016 Oct 6;6:34854. doi: 10.1038/srep34854.
Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape.
糖基磷脂酰肌醇锚定蛋白（GPI-APs）位于真菌细胞壁上，对于侵袭性感染至关重要。虽然以前已经研究过哺乳动物细胞中 GPI-APs 的肌醇去酰化作用的功能，但在真菌中肌醇去酰化的影响及其对宿主感染的意义在很大程度上仍未得到探索。本文描述了我们对白色念珠菌中 GPI-Aps 的肌醇去酰基酶 BST1 的鉴定，该酶对于 GPI-APs 的细胞壁附着和宿主感染至关重要。缺乏 BST1 的白色念珠菌（bst1Δ/Δ）与 GPI-APs 的细胞壁锚定严重受损以及随后未被掩盖的β-（1,3）-葡聚糖有关。与异常的细胞壁结构一致，bst1Δ/Δ 菌株没有表现出侵袭能力，并且可以被宿主免疫系统更有效地识别。此外，BST1 缺失突变体或表达 Bst1 变体的突变体没有表现出肌醇去酰化活性，并且在小鼠系统性念珠菌病模型中表现出严重的毒力减弱和有机定植减少。因此，Bst1 可以通过肌醇去酰化促进白色念珠菌中 GPI-APs 的细胞壁锚定，并且对于宿主侵袭和免疫逃避至关重要。
