Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Mol Syst Biol. 2010 Oct 19;6:422. doi: 10.1038/msb.2010.68.

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

Author information

  • 1Department of Bioengineering, University of California, San Diego, Powell-Focht Bioengineering Hall, La Jolla, CA, USA.

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.

PMID:
20959820
[PubMed - indexed for MEDLINE]
PMCID:
PMC2990636
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk