Septomics Research Center, Friedrich Schiller University, and Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Microbiol Spectr. 2023 Jun 15;11(3):e0049823. doi: 10.1128/spectrum.00498-23. Epub 2023 Apr 25.
Candida auris, a multidrug-resistant human fungal pathogen that causes outbreaks of invasive infections, emerged as four distinct geographical clades. Previous studies identified genomic and proteomic differences in nutrient utilization on comparison to Candida albicans, suggesting that certain metabolic features may contribute to C. auris emergence. Since no high-throughput clade-specific metabolic characterization has been described yet, we performed a phenotypic screening of C. auris strains from all 4 clades on 664 nutrients, 120 chemicals, and 24 stressors. We identified common and clade- or strain-specific responses, including the preferred utilization of various dipeptides as nitrogen source and the inability of the clade II isolate AR 0381 to withstand chemical stress. Further analysis of the metabolic properties of C. auris isolates showed robust growth on intermediates of the tricarboxylic acid cycle, such as citrate and succinic and malic acids. However, there was reduced or no growth on pyruvate, lactic acid, or acetate, likely due to the lack of the monocarboxylic acid transporter Jen1, which is conserved in most pathogenic species. Comparison of C. auris and C. albicans transcriptomes of cells grown on alternative carbon sources and dipeptides as a nitrogen source revealed common as well as species-unique responses. C. auris induced a significant number of genes with no ortholog in C. albicans, e.g., genes similar to the nicotinic acid transporter (alternative carbon sources) and to the oligopeptide transporter () family (dipeptides). Thus, C. auris possesses unique metabolic features which could have contributed to its emergence as a pathogen. Four main clades of the emerging, multidrug-resistant human pathogen Candida auris have been identified, and they differ in their susceptibilities to antifungals and disinfectants. Moreover, clade- and strain-specific metabolic differences have been identified, but a comprehensive overview of nutritional characteristics and resistance to various stressors is missing. Here, we performed high-throughput phenotypic characterization of C. auris on various nutrients, stressors, and chemicals and obtained transcriptomes of cells grown on selected nutrients. The generated data sets identified multiple clade- and strain-specific phenotypes and induction of C. auris-specific metabolic genes, showing unique metabolic properties. The presented work provides a large amount of information for further investigations that could explain the role of metabolism in emergence and pathogenicity of this multidrug-resistant fungus.
耳念珠菌是一种具有多重耐药性的人类真菌病原体，可引起侵袭性感染的爆发，它分为四个不同的地理分支。之前的研究发现，与白色念珠菌相比，耳念珠菌在营养物质利用方面存在基因组和蛋白质组差异，这表明某些代谢特征可能有助于耳念珠菌的出现。由于尚未描述针对特定分支的高通量代谢特征描述，我们对来自所有 4 个分支的耳念珠菌菌株在 664 种营养素、120 种化学物质和 24 种应激源上进行了表型筛选。我们确定了共同的和分支或菌株特异性的反应，包括各种二肽作为氮源的首选利用以及分支 II 分离株 AR 0381 无法承受化学应激的能力。对耳念珠菌分离株代谢特性的进一步分析表明，它们在三羧酸循环的中间体，如柠檬酸、琥珀酸和苹果酸上具有旺盛的生长能力。然而，在丙酮酸、乳酸或乙酸上的生长减少或不存在，这可能是由于缺乏单羧酸转运蛋白 Jen1 所致，该蛋白在大多数致病性物种中是保守的。比较在替代碳源和二肽作为氮源上生长的耳念珠菌和白色念珠菌的转录组，揭示了共同的和物种特有的反应。耳念珠菌诱导了大量在白色念珠菌中没有同源物的基因，例如，类似于烟酸转运蛋白（替代碳源）和寡肽转运蛋白（）家族（二肽）的基因。因此，耳念珠菌具有独特的代谢特征，这可能有助于其成为病原体。 已经确定了新兴的、具有多重耐药性的人类病原体耳念珠菌的四个主要分支，它们对抗真菌药物和消毒剂的敏感性不同。此外，已经确定了分支和菌株特异性的代谢差异，但缺乏对各种应激源的营养特征和抗性的全面概述。在这里，我们对各种营养素、应激源和化学品进行了耳念珠菌的高通量表型特征分析，并获得了在选定营养素上生长的细胞的转录组。生成的数据集确定了多个分支和菌株特异性表型，并诱导了耳念珠菌特异性代谢基因，显示出独特的代谢特性。所提供的工作为进一步研究提供了大量信息，这些研究可以解释代谢在这种多药耐药真菌的出现和致病性中的作用。
