Zavrel Martin, Majer Olivia, Kuchler Karl, Rupp Steffen
Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany.
Eukaryot Cell. 2012 Feb;11(2):129-40. doi: 10.1128/EC.05206-11. Epub 2011 Dec 2.
The Candida albicans transcription factor Efg1 is known to be involved in many different cellular processes, including morphogenesis, general metabolism, and virulence. Here we show that besides its manifold roles, Efg1 also has a prominent effect on cell wall structure and composition, strongly affecting the structural glucan part. Deletion of only one allele of EFG1 already results in severe phenotypes for cell wall biogenesis, comparable to those with deletion of both alleles, indicative of a severe haploinsufficiency for EFG1. The observed defects in structural setup of the cell wall, together with previously reported alterations in expression of cell surface proteins, result in altered immunogenic properties of strains with compromised Efg1 function. This is shown by interaction studies with macrophages and primary dendritic cells. The structural changes in the cell wall carbohydrate meshwork presented here, together with the manifold changes in cell wall protein composition and metabolism reported in other studies, contribute to the altered immune response mounted by innate immune cells and to the altered virulence phenotypes observed for strains lacking EFG1.
已知白色念珠菌转录因子Efg1参与许多不同的细胞过程,包括形态发生、一般代谢和毒力。在此我们表明,除了其多种作用外,Efg1对细胞壁结构和组成也有显著影响,强烈影响结构葡聚糖部分。仅缺失EFG1的一个等位基因就已导致细胞壁生物合成出现严重表型,与缺失两个等位基因的情况相当,表明EFG1存在严重的单倍体不足。观察到的细胞壁结构设置缺陷,连同先前报道的细胞表面蛋白表达改变,导致Efg1功能受损菌株的免疫原性特性发生改变。与巨噬细胞和原代树突状细胞的相互作用研究表明了这一点。此处呈现的细胞壁碳水化合物网络结构变化,连同其他研究报道的细胞壁蛋白质组成和代谢的多种变化,导致先天免疫细胞引发的免疫反应改变,以及缺乏EFG1的菌株所观察到的毒力表型改变。