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Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis

Øyås, Ove and Borrell, Sonia and Trauner, Andrej and Zimmermann, Michael and Feldmann, Julia and Liphardt, Thomas and Gagneux, Sebastien and Stelling, Jörg and Sauer, Uwe and Zampieri, Mattia. (2020) Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 117 (15). pp. 8494-8502.

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Official URL: https://edoc.unibas.ch/76439/

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Abstract

Human tuberculosis is caused by members of the; Mycobacterium tuberculosis; complex (MTBC) that vary in virulence and transmissibility. While genome-wide association studies have uncovered several mutations conferring drug resistance, much less is known about the factors underlying other bacterial phenotypes. Variation in the outcome of tuberculosis infection and diseases has been attributed primarily to patient and environmental factors, but recent evidence indicates an additional role for the genetic diversity among MTBC clinical strains. Here, we used metabolomics to unravel the effect of genetic variation on the strain-specific metabolic adaptive capacity and vulnerability. To define the functionality of single-nucleotide polymorphisms (SNPs) systematically, we developed a constraint-based approach that integrates metabolomic and genomic data. Our model-based predictions correctly classify SNP effects in pyruvate kinase and suggest a genetic basis for strain-specific inherent baseline susceptibility to the antibiotic; para; -aminosalicylic acid. Our method is broadly applicable across microbial life, opening possibilities for the development of more selective treatment strategies.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Borrell, Sonia and Trauner, Andrej and Feldmann, Julia and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Apr 2020 14:43
Deposited On:23 Apr 2020 14:43

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