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PMID: 20959820 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions.

Molecular systems biology ·Vol. 6 ·2010-10-19 ·Pages 422

Bordbar A, Lewis NE, Schellenberger J, Palsson BØ, Jamshidi N

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.

MeSH Terms
Adenosine Triphosphate Computational Biology/methods Computer Simulation Databases, Genetic Genes, Bacterial Host-Pathogen Interactions Humans Macrophages, Alveolar/metabolism,microbiology Metabolic Networks and Pathways Models, Biological Monte Carlo Method Mycobacterium tuberculosis/genetics,metabolism,pathogenicity Nitric Oxide/metabolism
Chemicals
Nitric Oxide Adenosine Triphosphate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bordbar Aarash
Department of Bioengineering, University of California, San Diego, Powell-Focht Bioengineering Hall, La Jolla, CA, USA.
Lewis Nathan E
Schellenberger Jan
Palsson Bernhard Ø
Jamshidi Neema
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2010.68
Published
2010-10-19
Pages
422
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2990636
Subset
IM
Grants
NHLBI NIH HHS · T32 HL007089 · United States
NIAID NIH HHS · Y1-AI-8401-01 · United States
NIGMS NIH HHS · GM068837 · United States
NIGMS NIH HHS · R01 GM068837 · United States
NIAID NIH HHS · Y01 AI008401 · United States
External Links
PubMed source DOI: 10.1038/msb.2010.68 PMC Full Text View journal details
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