English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  GSMN-TB : a web-based genome-scale network model of Mycobacterium tuberculosis metabolism

Beste, D. J., Hooper, T., Stewart, G., Bonde, B., Avignone-Rossa, C., Bushell, M. E., et al. (2007). GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism. Genome Biology, 8: R89. doi:10.1186/gb-2007-8-5-r89.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-98E0-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-8A3A-5
Genre: Journal Article

Files

show Files
hide Files
:
GenomeBiology_8_R89.pdf (Publisher version), 2MB
Name:
GenomeBiology_8_R89.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2007 Beste et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License

Locators

show

Creators

show
hide
 Creators:
Beste, D. J.1, Author
Hooper, T.1, Author
Stewart, G.1, Author
Bonde, B.1, Author
Avignone-Rossa, C.1, Author
Bushell, M. E.1, Author
Wheeler, P.2, Author
Klamt, S.3, Author              
Kierzek, A. M.1, Author
McFadden, J.1, Author
Affiliations:
1University of Surrey, School of Biomedical and Molecular Sciences, Stag Hill, Guildford, Surrey, UK, ou_persistent22              
2Tuberculosis Research Group, Veterinary Laboratories Agency (Weybridge), Addlestone UK, ou_persistent22              
3Systems Biology, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738155              

Content

show
hide
Free keywords: -
 Abstract: An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis. Results GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was constructed, consisting of 849 unique reactions and 739 metabolites, and involving 726 genes. The model was calibrated by growing Mycobacterium bovis bacille Calmette Guérin in continuous culture and steady-state growth parameters were measured. Flux balance analysis was used to calculate substrate consumption rates, which were shown to correspond closely to experimentally determined values. Predictions of gene essentiality were also made by flux balance analysis simulation and were compared with global mutagenesis data for M. tuberculosis grown in vitro. A prediction accuracy of 78% was achieved. Known drug targets were predicted to be essential by the model. The model demonstrated a potential role for the enzyme isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was experimentally verified. An interactive web-based version of the model is available. Conclusion The GSMN-TB model successfully simulated many of the growth properties of M. tuberculosis. The model provides a means to examine the metabolic flexibility of bacteria and predict the phenotype of mutants, and it highlights previously unexplored features of M. tuberculosis metabolism.

Details

show
hide
Language(s): eng - English
 Dates: 2007
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1186/gb-2007-8-5-r89
eDoc: 320932
Other: 28/07
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Genome Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 8 Sequence Number: R89 Start / End Page: - Identifier: -