Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions
Abstract Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome‐scale metabolic models have shown utility in integrating ‐omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis o...
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.68 |
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| author | Aarash Bordbar Nathan E Lewis Jan Schellenberger Bernhard Ø Palsson Neema Jamshidi |
| author_facet | Aarash Bordbar Nathan E Lewis Jan Schellenberger Bernhard Ø Palsson Neema Jamshidi |
| author_sort | Aarash Bordbar |
| collection | DOAJ |
| description | Abstract Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome‐scale metabolic models have shown utility in integrating ‐omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis of host–pathogen interactions using in silico mass‐balanced, genome‐scale models has not been performed. We, therefore, constructed a cell‐specific alveolar macrophage model, iAB‐AMØ‐1410, from the global human metabolic reconstruction, Recon 1. The model successfully predicted experimentally verified ATP and nitric oxide production rates in macrophages. This model was then integrated with an M. tuberculosis H37Rv model, iNJ661, to build an integrated host–pathogen genome‐scale reconstruction, iAB‐AMØ‐1410‐Mt‐661. The integrated host–pathogen network enables simulation of the metabolic changes during infection. The resulting reaction activity and gene essentiality targets of the integrated model represent an altered infectious state. High‐throughput data from infected macrophages were mapped onto the host–pathogen network and were able to describe three distinct pathological states. Integrated host–pathogen reconstructions thus form a foundation upon which understanding the biology and pathophysiology of infections can be developed. |
| format | Article |
| id | doaj-art-ee29f60a9ffd453c85e53e45a7737935 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2010-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-ee29f60a9ffd453c85e53e45a77379352025-08-24T12:00:41ZengSpringer NatureMolecular Systems Biology1744-42922010-10-016111410.1038/msb.2010.68Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructionsAarash Bordbar0Nathan E Lewis1Jan Schellenberger2Bernhard Ø Palsson3Neema Jamshidi4Department of Bioengineering, University of California, San Diego, Powell‐Focht Bioengineering HallDepartment of Bioengineering, University of California, San Diego, Powell‐Focht Bioengineering HallDepartment of Bioengineering, Bioinformatics Program, University of California, San Diego, Powell‐Focht Bioengineering HallDepartment of Bioengineering, University of California, San Diego, Powell‐Focht Bioengineering HallDepartment of Bioengineering, University of California, San Diego, Powell‐Focht Bioengineering HallAbstract Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome‐scale metabolic models have shown utility in integrating ‐omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis of host–pathogen interactions using in silico mass‐balanced, genome‐scale models has not been performed. We, therefore, constructed a cell‐specific alveolar macrophage model, iAB‐AMØ‐1410, from the global human metabolic reconstruction, Recon 1. The model successfully predicted experimentally verified ATP and nitric oxide production rates in macrophages. This model was then integrated with an M. tuberculosis H37Rv model, iNJ661, to build an integrated host–pathogen genome‐scale reconstruction, iAB‐AMØ‐1410‐Mt‐661. The integrated host–pathogen network enables simulation of the metabolic changes during infection. The resulting reaction activity and gene essentiality targets of the integrated model represent an altered infectious state. High‐throughput data from infected macrophages were mapped onto the host–pathogen network and were able to describe three distinct pathological states. Integrated host–pathogen reconstructions thus form a foundation upon which understanding the biology and pathophysiology of infections can be developed.https://doi.org/10.1038/msb.2010.68computational biologyhost‐pathogenMycobacterium tuberculosissystems biologymacrophage |
| spellingShingle | Aarash Bordbar Nathan E Lewis Jan Schellenberger Bernhard Ø Palsson Neema Jamshidi Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions Molecular Systems Biology computational biology host‐pathogen Mycobacterium tuberculosis systems biology macrophage |
| title | Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions |
| title_full | Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions |
| title_fullStr | Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions |
| title_full_unstemmed | Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions |
| title_short | Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions |
| title_sort | insight into human alveolar macrophage and m tuberculosis interactions via metabolic reconstructions |
| topic | computational biology host‐pathogen Mycobacterium tuberculosis systems biology macrophage |
| url | https://doi.org/10.1038/msb.2010.68 |
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