Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms

Candida albicans biofilms form complex structures that shield the fungus from antifungal agents and host immune responses, which is particularly problematic for the treatment of severe candidiasis. The increasing thickness and formation of hyphal networks of growing biofilms result in nutrient and gas shifts that lead to sequential metabolic rearrangements. This study provides very comprehensive insights into the molecular and metabolic mechanisms of C. albicans biofilm maturation by combining three state-of-the-art omics techniques. Adaptive nutrient and stress responses enabled wild type biofilms to mature in an increasingly nutrient- and oxygen-limited environment. C. albicans biofilms lacking Stp2, a transcriptional regulator of amino acid uptake, underwent extensive transcriptional changes resulting in metabolic adaptations such as broad restructuring of nitrogen metabolism, glucose uptake, and acquisition of alternative nutrients. This finding underscores the indispensable need for amino acid supply during biofilm development and emphasizes the tremendous metabolic flexibility to adapt to changing environments that have made C. albicans a successful opportunistic pathogen.

白色念珠菌（Candida albicans）生物膜可形成复杂结构，使该真菌得以躲避抗真菌剂（antifungal agents）与宿主免疫应答（host immune responses），这对重症念珠菌病（severe candidiasis）的治疗而言尤为棘手。正在成熟的生物膜其厚度不断增加、菌丝网络（hyphal networks）形成，会引发营养与气体环境改变，进而导致有序的代谢重排（metabolic rearrangements）。本研究结合三项前沿组学技术（omics techniques），对白色念珠菌生物膜成熟过程中的分子与代谢机制进行了全面深入的解析。野生型生物膜可通过适应性营养与应激响应，在营养与氧气逐渐受限的环境中完成成熟过程。缺失氨基酸摄取转录调控因子（transcriptional regulator）Stp2的白色念珠菌生物膜会发生广泛的转录变化（transcriptional changes），进而产生代谢适应性改变，包括氮代谢（nitrogen metabolism）的大规模重构、葡萄糖摄取（glucose uptake）以及替代营养物质（alternative nutrients）的获取等。该研究结果凸显了氨基酸供给在生物膜发育过程中的不可或缺性，同时强调了白色念珠菌为适应多变环境所具备的极强代谢灵活性——这一特性也使其成为了成功的条件致病菌（opportunistic pathogen）。