Department of Medicine, Section of Infectious Diseases, University of Wisconsin-Madison, Madison, WI, USA.
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
Nat Commun. 2021 Oct 29;12(1):6235. doi: 10.1038/s41467-021-26525-z.
The fungal pathogen Candida albicans can form biofilms that protect it from drugs and the immune system. The biofilm cells release extracellular vesicles (EVs) that promote extracellular matrix formation and resistance to antifungal drugs. Here, we define functions for numerous EV cargo proteins in biofilm matrix assembly and drug resistance, as well as in fungal cell adhesion and dissemination. We use a machine-learning analysis of cargo proteomic data from mutants with EV production defects to identify 63 candidate gene products for which we construct mutant and complemented strains for study. Among these, 17 mutants display reduced biofilm matrix accumulation and antifungal drug resistance. An additional subset of 8 cargo mutants exhibit defects in adhesion and/or dispersion. Representative cargo proteins are shown to function as EV cargo through the ability of exogenous wild-type EVs to complement mutant phenotypic defects. Most functionally assigned cargo proteins have roles in two or more of the biofilm phases. Our results support that EVs provide community coordination throughout biofilm development in C. albicans.
真菌病原体白色念珠菌可以形成生物膜，从而使其免受药物和免疫系统的侵害。生物膜细胞释放出细胞外囊泡 (EVs)，促进细胞外基质的形成和对抗真菌药物的耐药性。在这里，我们确定了生物膜基质组装和抗真菌药物耐药性、真菌细胞黏附和传播中众多 EV 货物蛋白的功能。我们使用从 EV 产生缺陷突变体的货物蛋白质组学数据的机器学习分析，来识别 63 个候选基因产物，我们为此构建了突变体和互补菌株进行研究。其中，17 个突变体显示生物膜基质积累减少和抗真菌药物耐药性降低。另外一组 8 个货物突变体表现出黏附和/或分散缺陷。通过外源性野生型 EV 补充突变表型缺陷的能力，证明代表性货物蛋白作为 EV 货物发挥作用。大多数功能分配的货物蛋白在生物膜发育的两个或更多阶段中发挥作用。我们的结果支持 EVs 在白色念珠菌生物膜发育过程中提供群落协调。
