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Cell Host Microbe. 2013 Jan 16;13(1):108-17. doi: 10.1016/j.chom.2012.11.011. Epub 2013 Jan 16.

Host metabolism regulates intracellular growth of Trypanosoma cruzi.

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1
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Building I, Room 817, Boston, MA 02115, USA.

Abstract

Metabolic coupling of intracellular pathogens with host cells is essential for successful colonization of the host. Establishment of intracellular infection by the protozoan Trypanosoma cruzi leads to the development of human Chagas' disease, yet the functional contributions of the host cell toward the infection process remain poorly characterized. Here, a genome-scale functional screen identified interconnected metabolic networks centered around host energy production, nucleotide metabolism, pteridine biosynthesis, and fatty acid oxidation as key processes that fuel intracellular T. cruzi growth. Additionally, the host kinase Akt, which plays essential roles in various cellular processes, was critical for parasite replication. Targeted perturbations in these host metabolic pathways or Akt-dependent signaling pathways modulated the parasite's replicative capacity, highlighting the adaptability of this intracellular pathogen to changing conditions in the host. These findings identify key cellular process regulating intracellular T. cruzi growth and illuminate the potential to leverage host pathways to limit T. cruzi infection.

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PMID:
23332160
PMCID:
PMC3560928
DOI:
10.1016/j.chom.2012.11.011
[Indexed for MEDLINE]
Free PMC Article
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