Baart Gino J E, Zomer Bert, de Haan Alex, van der Pol Leo A, Beuvery E Coen, Tramper Johannes, Martens Dirk E
Unit Research & Development, Netherlands Vaccine Institute (NVI), PO Box 457, 3720 AL Bilthoven, The Netherlands.
Genome Biol. 2007;8(7):R136. doi: 10.1186/gb-2007-8-7-r136.
Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years.
Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested successfully in batch and chemostat cultures.
The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.
脑膜炎奈瑟菌是一种可感染人类宿主内不同部位的人类病原体。脑膜炎奈瑟菌引起的主要疾病可导致死亡和残疾，尤其是在幼儿中。一般来说，最近关于脑膜炎奈瑟菌的大多数研究都集中在潜在抗原及其功能、免疫原性和致病机制上。在过去25年里，关于奈瑟菌初级代谢的研究很少。
利用B群脑膜炎奈瑟菌的基因组数据库以及文献中的生化和生理信息，我们构建了一个脑膜炎奈瑟菌初级代谢的基因组规模通量模型。使用恒化器培养中的通量平衡分析检查了从基因组规模代谢网络导出的简化代谢网络的有效性。通过计算机模拟实验获得了一些有用的预测结果，包括底物偏好。设计了一种用于脑膜炎奈瑟菌生长的基本培养基，并在分批培养和恒化器培养中成功进行了测试。
经过验证的代谢模型描述了脑膜炎奈瑟菌在恒化器中稳态下的初级代谢。基因组规模模型很有价值，因为它提供了一个框架来整体研究脑膜炎奈瑟菌的代谢或其某些方面，也可用于疫苗工艺开发（例如生长培养基的设计）。主要代谢途径（即磷酸戊糖途径和恩特纳-杜德洛夫途径）的通量分布表明，大部分丙酮酸（69%）是通过ED裂解合成的，这一发现与文献报道非常吻合。
