Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

Gino JE Baart¹^,3 , Bert Zomer¹ , Alex de Haan¹ , Leo A van der Pol¹ , E Coen Beuvery² , Johannes Tramper³ and Dirk E Martens³

¹Unit Research & Development, Netherlands Vaccine Institute (NVI), PO Box 457, 3720 AL Bilthoven, The Netherlands

²PAT Consultancy, Kerkstraat 66, 4132 BG Vianen, The Netherlands

³Food and Bioprocess Engineering Group, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands

author email corresponding author email

Genome Biology 2007, 8:R136doi:10.1186/gb-2007-8-7-r136


Published:	6 July 2007

Subject areas: Microbiology and parasitology, Bioinformatics

Abstract

Background

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.

Results

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 succesfully in batch and chemostat cultures.

Conclusion

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.