Genome-Scale Metabolic Model of Xanthomonas phaseoli pv. manihotis: An Approach to Elucidate Pathogenicity at the Metabolic Level

Genome-Scale Metabolic Model of Xanthomonas phaseoli pv. manihotis: An Approach to Elucidate Pathogenicity at the Metabolic Level
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DOI:
10.3389/fgene.2020.00837
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发表时间:
2020-08-11
影响因子:
3.7
通讯作者:
Bernal, Adriana
Bernal, Adriana
中科院分区:
生物学3区
文献类型:
--
作者:
Botero, David;Monk, Jonathan;Bernal, Adriana

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菜豆黄单胞菌致病变种木薯(Manihotis)(Xpm)是木薯细菌性枯萎病(cassava bacterial blight)的病原体,木薯细菌性枯萎病是木薯中最重要的细菌性疾病。除了对黄原胶生物合成途径的阐明外,关于黄单胞菌的代谢及其在致病过程中的相关性的知识很少。在这里,我们报告的Xpm代谢的基因组规模模型的重建和它提供的见解植物病原体相互作用。iXpm 1,556模型显示了1,556个反应,1,527种化合物和890个基因。中心氨基酸和碳水化合物代谢以及Xpm的黄原胶生物合成的代谢图使用Spectrophoter(https://escher.github.io/)重建,以指导策展过程并用于进一步分析。使用Xpm的突变体的RNA-seq数据约束该模型用于群体感应(QS),并且这些数据用于构建两种菌株(野生型和QS突变体)的代谢的背景特异性模型(CSM)。CSM和通量平衡分析用于深入了解致病性、黄原胶生物合成和QS机制。在CSM之间,共有653个反应;独特的反应属于嘌呤、嘧啶和氨基酸代谢。替代的目标函数被用来证明黄原胶的生物合成和生长之间的权衡和重新分配的生物合成过程中的资源。QS改变的重要特征包括碳水化合物代谢、NAD(P)(+)平衡和脂肪酸延长。在这项工作中,我们模拟了黄原胶的生物合成和QS过程及其对细菌代谢的影响。该模型将有助于研究宿主-病原体相互作用的研究人员,并将为该种和其他黄单胞菌属物种的感染机制提供见解。
Xanthomonas phaseoli pv. manihotis (Xpm) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of Xanthomonas and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of Xpm metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of Xpm, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of Xpm for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)(+) balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other Xanthomonas species.