ArticlePloS one2013
Systems-based approaches to probing metabolic variation within the Mycobacterium tuberculosis complex.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 75 citations in OpenAlex.
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- Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022Review
- Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.Molecular systems biology · 2021Article
- Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches.Frontiers in immunology · 2021Review
- Metabolomics reveals that the cAMP receptor protein regulates nitrogen and peptidoglycan synthesis inRSC advances · 2020Article
- GSMN-ML- a genome scale metabolic network reconstruction of the obligate human pathogen Mycobacterium leprae.PLoS neglected tropical diseases · 2020Article
- A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks.PLoS computational biology · 2020Article
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- Small RNA Mcr11 requires the transcription factor AbmR for stable expression and regulates genes involved in the central metabolism of Mycobacterium tuberculosis.Molecular microbiology · 2020Article
- Genome-Scale Metabolic Modeling for Unraveling Molecular Mechanisms of High Threat Pathogens.Frontiers in cell and developmental biology · 2020Review
- Intracellular Mycobacterium tuberculosis Exploits Multiple Host Nitrogen Sources during Growth in Human Macrophages.Cell reports · 2019Article
- Modeling Host-Pathogen Interaction to Elucidate the Metabolic Drug Response of IntracellularFrontiers in cellular and infection microbiology · 2019Article
- Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis.Nature reviews. Microbiology · 2018Review
- Updated and standardized genome-scale reconstruction of Mycobacterium tuberculosis H37Rv, iEK1011, simulates flux states indicative of physiological conditions.BMC systems biology · 2018Article
- Modeling the Metabolic State ofFrontiers in cellular and infection microbiology · 2018Article
- Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection.BMC systems biology · 2017Article
- PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis.PLoS pathogens · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Mycobacterium tuberculosis complex includes bovine and human strains of the tuberculosis bacillus, including Mycobacterium tuberculosis, Mycobacterium bovis and the Mycobacterium bovis BCG vaccine strain. M. bovis has evolved from a M. tuberculosis-like ancestor and is the ancestor of the BCG vaccine. The pathogens demonstrate distinct differences in virulence, host range and metabolism, but the role of metabolic differences in pathogenicity is poorly understood. Systems biology approaches have been used to investigate the metabolism of M. tuberculosis, but not to probe differences between tuberculosis strains. In this study genome scale metabolic networks of M. bovis and M. bovis BCG were constructed and interrogated, along with a M. tuberculosis network, to predict substrate utilisation, gene essentiality and growth rates. The models correctly predicted 87-88% of high-throughput phenotype data, 75-76% of gene essentiality data and in silico-predicted growth rates matched measured rates. However, analysis of the metabolic networks identified discrepancies between in silico predictions and in vitro data, highlighting areas of incomplete metabolic knowledge. Additional experimental studies carried out to probe these inconsistencies revealed novel insights into the metabolism of these strains. For instance, that the reduction in metabolic capability observed in bovine tuberculosis strains, as compared to M. tuberculosis, is not reflected by current genetic or enzymatic knowledge. Hence, the in silico networks not only successfully simulate many aspects of the growth and physiology of these mycobacteria, but also provide an invaluable tool for future metabolic studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.