Tuberculosis pathogenesis, virulence and persistence

The EU-funded project 'Systems biology of Mycobacterium tuberculosis' (SYSTEMTB) developed a systems biology framework for model-based studies on the causal agent, MTb. Understanding interactions of MTb with the host is needed for the development of novel and cost-effective strategies to combat TB.

SYSTEMTB generated quantitative data sets of MTb describing transcriptomics, proteomics, metabolomics, structural genomics, lipidomics and glycomics. Computer models with an emphasis on metabolism, regulatory networks and transcription regulation were developed.

Identification of new possible targets for therapeutic intervention based on computer modelling was an important part of the project. These approaches provide a rational framework for understanding of mycobacterial physiology during infection.

The project led to advanced understanding of physical interactions, structures, functions and localisations of MTb proteins. A database on the SYSTEMTB website allows the scientific community easy access to the fluorescent-tagged MTb library. The database integrates the MTb clones with their protein localisation images. More than 2 000 clones of the library have been amplified and handed to consortium members.

Several resources were published as a result of the project. Thus, the PeptideAtlas database is to date the most extensive collection of proteomic databases for MTb. The SRMAtlas database contains mass spectrometric assays for the entire proteome of MTb. The PASSEL database contains experimental evidence for every protein identified by the selected reaction monitoring (SRM) assays deposited in the SRMAtlas.

As a result of SYSTEMTB, a consensus genome-scale constrain-based model of the metabolism and transport of MTb was generated. This model is currently the most comprehensive model of metabolism of MTb with 1 179 reactions, 874 genes and 83 % of reactions with a gene association. The key to success of the SYSTEMTB project was the integration of bioinformatics, structural and functional studies.