The mitA gene of Aspergillus fumigatus is required for mannosylation of inositol-phosphorylceramide, but is dispensable for pathogenicity
The mitA gene of Aspergillus fumigatus is required for mannosylation of inositol-phosphorylceramide, but is dispensable for pathogenicity
复制标题
DOI：
10.1016/j.fgb.2009.10.001
复制
发表时间：
2010-02-01
影响因子：
3
通讯作者：
Ebel, Frank
中科院分区：
文献类型：
--
作者：
Kotz, Andrea;Wagener, Johannes;Ebel, Frank
GDP-甘露糖：肌醇-磷酰神经酰胺(MIPC)衍生的鞘糖脂是白色念珠菌和烟曲霉的重要病原体相关分子模式(PAMP)。MIPC转移酶是合成MIPC所必需的，但到目前为止只在酿酒酵母和白色念珠菌中进行了研究。在此，我们已经确定MITA是烟曲霉菌中唯一的MIPC转移酶。Delta Mita突变体缺乏MIPC和MIPC衍生的糖鞘糖脂，并积累前体IPC。突变体生长正常，细胞壁和细胞膜组织无缺陷，对不同的逆境具有正常的抗性。然而，它对高浓度的钙离子很敏感，特别是在萌发期间。Delta Mita突变体分生孢子在正常生长条件下的萌发也会减慢，但该突变体在系统感染模型中的毒力和在巨噬细胞中触发细胞因子反应的能力都没有受到损害，这证明了MIPC衍生的糖鞘糖脂作为重要的烟曲霉菌PAMPs的作用。(C)2009 Elsevier Inc.保留所有权利。
GDP-mannose:inositol-phosphorylceramide (MIPC)-derived glycosphingolipids are important pathogen-associated molecular patterns (PAMP) of Candida albicans and according to recently published data also of Aspergillus fumigatus. MIPC transferases are essential for the synthesis of MIPC, but have so far been studied only in Saccharomyces cerevisiae and C. albicans. Here, we have identified MitA as the only MIPC transferase in A. fumigatus. The Delta mitA mutant lacks MIPC and MIPC-derived glycosphingolipids and accumulates the precursor IPC. The mutant grows normally, shows no defects in cell wall or membrane organization and a normal resistance to different stressors. It is, however, sensitive to high Ca2+ concentrations, especially during germination. Germination of Delta mitA mutant conidia is also decelerated under normal growth conditions, but neither the virulence of this mutant in a systemic model of infection nor its ability to trigger a cytokine response in macrophages is impaired, arguing against a role of MIPC-derived glycosphingolipids as important A. fumigatus PAMPs. (c) 2009 Elsevier Inc. All rights reserved.