Abstract：
Candida auris is an emerging human pathogen, associated with antifungal drug resistance and hospital candidiasis outbreaks. In this work, we present iRV973, the first reconstructed Genome-scale metabolic model (GSMM) for C. auris. The model was manually curated and experimentally validated, being able to accurately predict the specific growth rate of C. auris and the utilization of several sole carbon and nitrogen sources. The model was compared to GSMMs available for other pathogenic Candida species and exploited as a platform for cross-species comparison, aiming the analysis of their metabolic features and the identification of potential new antifungal targets common to the most prevalent pathogenic Candida species. From a metabolic point of view, we were able to identify unique enzymes in C. auris in comparison with other Candida species, which may represent unique metabolic features. Additionally, 50 enzymes were identified as potential drug targets, given their essentiality in conditions mimicking human serum, common to all four different Candida models analysed. These enzymes represent interesting drug targets for antifungal therapy, including some known targets of antifungal agents used in clinical practice, but also new potential drug targets without any human homolog or drug association in Candida species.
摘要：
耳念珠菌是一种新兴的人类病原体，与抗真菌药物耐药性和医院念珠菌病暴发有关。在这项工作中,我们提出了iRV973，第一个重建的基因组尺度代谢模型（GSMM）。该模型是手动策划和实验验证的，能够准确预测C.auris的特定生长速率以及几种唯一碳源和氮源的利用。将该模型与其他致病性念珠菌物种的GSMM进行比较，并将其用作跨物种比较的平台。旨在分析其代谢特征，并鉴定最常见的致病性念珠菌的潜在新抗真菌靶标。从新陈代谢的角度来看，与其他念珠菌相比，我们能够在C.auris中鉴定出独特的酶，这可能代表独特的代谢特征。此外,50种酶被确定为潜在的药物靶标，鉴于它们在模仿人类血清的条件下的重要性，分析了所有四种不同念珠菌模型的共同点。这些酶代表了抗真菌治疗的有趣药物靶标，有些是临床实践中使用的抗真菌药物的已知目标，但是其他新的潜在药物靶标也在念珠菌物种中没有任何人类同源物或药物关联的情况下脱颖而出。
