GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen Mycobacterium leprae
GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen Mycobacterium leprae
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GSMN-ML-人类专性病原体麻风分枝杆菌的基因组规模代谢网络重建
DOI：
10.1101/819508
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Borah K
中科院分区：
文献类型：
--
作者：
Borah K
由麻风分枝杆菌引起的麻风已困扰人类数千年，今天仍有200万至300万人患病、残疾和被污名化。虽然有有效的治疗方法，但这种疾病的发病率几十年来一直保持不变，因此迫切需要新的方法，如疫苗或新药来控制。然而，由于病原体的专性细胞内生活方式以及它从未在体外生长的事实，研究受到阻碍。因此，尽管可以获得其完整的基因组序列，但有关病原体生物学的基本问题，例如其代谢，在很大程度上仍未被探索。为了探索麻风病芽孢杆菌的代谢机制，并长期寻找病原菌体外生长的培养基，我们构建了麻风病芽孢杆菌的硅基因组尺度代谢模型GSMN-ML。该模型用于探索病原菌在氨基酸、葡萄糖、甘油和代谢中间体等多种营养来源下的生长和生物量生产能力。我们还使用该模型分析了来自mm的RNA-seq数据。并进行差异可产性分析，以确定在病原体细胞内生长过程中似乎活跃的代谢途径，包括中心碳代谢、辅助因子、脂质、氨基酸、核苷酸和细胞壁合成途径。因此，GSMN-ML模型是一种有用的硅工具，可用于探索麻风病芽孢杆菌的代谢，分析功能基因组实验数据，预测芽孢杆菌体外生长所需的营养物质，并确定新的药物靶点。
Leprosy, caused byMycobacterium leprae, has plagued humanity for thousands of years and continues to cause morbidity, disability and stigmatization in two to three million people today. Although effective treatment is available, the disease incidence has remained approximately constant for decades so new approaches, such as vaccine or new drugs, are urgently needed for control. Research is however hampered by the pathogen’s obligate intracellular lifestyle and the fact that it has never been grownin vitro. Consequently, despite the availability of its complete genome sequence, fundamental questions regarding the biology of the pathogen, such as its metabolism, remain largely unexplored. In order to explore the metabolism of the leprosy bacillus with a long-term aim of developing a medium to grow the pathogenin vitro, we reconstructed anin silicogenome scale metabolic model of the bacillus, GSMN-ML. The model was used to explore the growth and biomass production capabilities of the pathogen with a range of nutrient sources, such as amino acids, glucose, glycerol and metabolic intermediates. We also used the model to analyze RNA-seq data fromM.lepraegrown in mouse foot pads, and performed Differential Producibility Analysis to identify metabolic pathways that appear to be active during intracellular growth of the pathogen, which included pathways for central carbon metabolism, co-factor, lipids, amino acids, nucleotides and cell wall synthesis. The GSMN-ML model is thereby a usefulin silicotool that can be used to explore the metabolism of the leprosy bacillus, analyze functional genomic experimental data, generate predictions of nutrients required for growth of the bacillusin vitroand identify novel drug targets.
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影响因子：
0.6
作者：
E. Spierings;T. Boer;L. Zulianello;T. Ottenhoff
通讯作者：
E. Spierings;T. Boer;L. Zulianello;T. Ottenhoff
麻风病：关于消除、减轻疾病负担和未来研究的回顾。
影响因子：
0.6
作者：
Casandra Chaptini;G. Marshman
通讯作者：
G. Marshman
麻风分枝杆菌的培养问题：最近实验工作评估标准的综述。
DOI：
--
发表时间：
1977
期刊：
Leprosy in India
影响因子：
--
作者：
S. Pattyn
通讯作者：
S. Pattyn
米黄单胞菌 (Xanthomonas oryzae pv.) 的 d-丙氨酸-d-丙氨酸连接酶的晶体结构。
影响因子：
3.9
作者：
T. Doan;Jin;H. Ngo;H. Tran;S. Cha;Kyung Min Chung;Kim;Y. Ahn;L. Kang
通讯作者：
L. Kang
影响因子：
64.8
作者：
Cole, ST;Brosch, R;Barrell, BG
通讯作者：
Barrell, BG