Charusanti Pep, Chauhan Sadhana, McAteer Kathleen, Lerman Joshua A, Hyduke Daniel R, Motin Vladimir L, Ansong Charles, Adkins Joshua N, Palsson Bernhard O
Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
BMC Syst Biol. 2011 Oct 13;5:163. doi: 10.1186/1752-0509-5-163.
Yersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era. Metabolism in Y. pestis displays remarkable flexibility and robustness, allowing the bacterium to proliferate in both warm-blooded mammalian hosts and cold-blooded insect vectors such as fleas.
Here we report a genome-scale reconstruction and mathematical model of metabolism for Y. pestis CO92 and supporting experimental growth and metabolite measurements. The model contains 815 genes, 678 proteins, 963 unique metabolites and 1678 reactions, accurately simulates growth on a range of carbon sources both qualitatively and quantitatively, and identifies gaps in several key biosynthetic pathways and suggests how those gaps might be filled. Furthermore, our model presents hypotheses to explain certain known nutritional requirements characteristic of this strain.
Y. pestis continues to be a dangerous threat to human health during modern times. The Y. pestis genome-scale metabolic reconstruction presented here, which has been benchmarked against experimental data and correctly reproduces known phenotypes, provides an in silico platform with which to investigate the metabolism of this important human pathogen.
鼠疫耶尔森菌是一种革兰氏阴性菌，可引发鼠疫，这种疾病在历史上与中世纪欧洲的黑死病以及现代的几次疫情爆发有关。鼠疫耶尔森菌的新陈代谢表现出显著的灵活性和稳健性，使该细菌能够在温血哺乳动物宿主和冷血昆虫载体（如跳蚤）中增殖。
在此，我们报告了鼠疫耶尔森菌CO92的全基因组规模的新陈代谢重建和数学模型，以及支持性的实验生长和代谢物测量。该模型包含815个基因、678种蛋白质、963种独特的代谢物和1678个反应，能定性和定量地准确模拟在一系列碳源上的生长，并识别出几个关键生物合成途径中的缺口，并提出填补这些缺口的可能方式。此外，我们的模型提出了一些假设来解释该菌株某些已知的营养需求特征。
在现代，鼠疫耶尔森菌仍然是对人类健康的危险威胁。这里呈现的鼠疫耶尔森菌全基因组规模的代谢重建，已根据实验数据进行了基准测试，并正确再现了已知表型，提供了一个计算机模拟平台，用以研究这种重要人类病原体的新陈代谢。
