Metabolic reconstruction of the human pathogen Candida auris: using a cross-species approach for drug target prediction.

IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Romeu Viana, Tiago Carreiro, Diogo Couceiro, Oscar Dias, Isabel Rocha, Miguel Cacho Teixeira
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引用次数: 0

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.

人类病原体耳念珠菌的代谢重建:使用跨物种方法预测药物靶点。
耳念珠菌是一种新出现的人类病原体,与抗真菌耐药性和医院念珠菌感染暴发有关。在这项工作中,我们提出了iRV973,这是第一个重建的金黄色葡萄球菌基因组级代谢模型(GSMM)。该模型经过人工策划和实验验证,能够准确预测金合欢的比生长速率以及几种唯一碳和氮来源的利用率。将该模型与可用于其他致病性念珠菌物种的GSMM进行比较,并将其作为跨物种比较的平台,旨在分析其代谢特征,并确定最常见的致病性念珠菌常见的潜在新抗真菌靶标。从代谢的角度来看,与其他念珠菌物种相比,我们能够在耳念珠菌中鉴定出独特的酶,这可能代表了独特的代谢特征。此外,考虑到50种酶在模拟人类血清的条件下的重要性,它们被确定为潜在的药物靶点,这是所分析的所有四种不同念珠菌模型所共有的。这些酶代表了抗真菌治疗的有趣药物靶点,其中一些是临床实践中使用的抗真菌药物的已知靶点,但其他新的潜在药物靶点也很突出,在念珠菌中没有任何人类同源物或药物关联。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEMS yeast research
FEMS yeast research 生物-生物工程与应用微生物
CiteScore
5.70
自引率
6.20%
发文量
54
审稿时长
1 months
期刊介绍: FEMS Yeast Research offers efficient publication of high-quality original Research Articles, Mini-reviews, Letters to the Editor, Perspectives and Commentaries that express current opinions. The journal will select for publication only those manuscripts deemed to be of major relevance to the field and generally will not consider articles that are largely descriptive without insights on underlying mechanism or biology. Submissions on any yeast species are welcome provided they report results within the scope outlined below and are of significance to the yeast field.
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