Viana Romeu, Dias Oscar, Lagoa Davide, Galocha Mónica, Rocha Isabel, Teixeira Miguel Cacho
Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal.
Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Instituto Superior Técnico, 1049-001 Lisbon, Portugal.
J Fungi (Basel). 2020 Sep 11;6(3):171. doi: 10.3390/jof6030171.
is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for , iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of , possibly guiding the identification of new drug targets to tackle human candidiasis.
是最具影响力的真菌病原体之一,也是侵袭性念珠菌病最常见的病因,侵袭性念珠菌病的死亡率非常高。随着多重耐药临床分离株频率的上升,识别新的药物靶点和新药对于克服治疗失败的增加至关重要。在本研究中,提出了第一个经过验证的的全基因组规模代谢模型iRV781。该模型由1221个反应、926个代谢物、781个基因和四个区室组成。该模型使用开源软件工具4.0.2重建。它以成熟的系统生物学标记语言(SBML)格式提供,因此可在大多数代谢工程平台(如OptFlux或COBRA)中使用。该模型经过验证,与实验数据相比,在预测利用不同碳源和氮源的能力时证明是准确的。最后,通过比较已知药物靶点和在模拟人类宿主的条件下对基因必需性的预测,将这个全基因组规模的代谢重建作为识别药物靶点的平台进行了测试。总之,该模型为全面阐明的代谢潜力提供了一个有前景的平台,可能指导识别治疗人类念珠菌病的新药物靶点。