Metabolic investigation of host/pathogen interaction using MS2-infected Escherichia coli

Jain, Rishi; Srivastava, Ranjan

doi:10.1186/1752-0509-3-121

Title: Metabolic investigation of host/pathogen interaction using MS2-infected Escherichia coli

Journal Article · 29 December 2009 · BMC Systems Biology

DOI: https://doi.org/10.1186/1752-0509-3-121 · OSTI ID:1626642

Jain, Rishi ^[1]; Srivastava, Ranjan ^[2]

University of Connecticut, Storrs, CT (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); DOE/OSTI
University of Connecticut, Storrs, CT (United States)

RNA viruses are responsible for a variety of illnesses among people, including but not limited to the common cold, the flu, HIV, and ebola. Developing new drugs and new strategies for treating diseases caused by these viruses can be an expensive and time-consuming process. Mathematical modeling may be used to elucidate host-pathogen interactions and highlight potential targets for drug development, as well providing the basis for optimizing patient treatment strategies. The purpose of this work was to determine whether a genome-scale modeling approach could be used to understand how metabolism is impacted by the host-pathogen interaction during a viral infection. Escherichia coli/MS2 was used as the host-pathogen model system as MS2 is easy to work with, harmless to humans, but shares many features with eukaryotic viruses. In addition, the genome-scale metabolic model of E. coli is the most comprehensive model at this time. Employing a metabolic modeling strategy known as "flux balance analysis" coupled with experimental studies, we were able to predict how viral infection would alter bacterial metabolism. Based on our simulations, we predicted that cell growth and biosynthesis of the cell wall would be halted. Furthermore, we predicted a substantial increase in metabolic activity of the pentose phosphate pathway as a means to enhance viral biosynthesis, while a break down in the citric acid cycle was predicted. Also, no changes were predicted in the glycolytic pathway. Through our approach, we have developed a technique of modeling virus-infected host metabolism and have investigated the metabolic effects of viral infection. These studies may provide insight into how to design better drugs. They also illustrate the potential of extending such metabolic analysis to higher order organisms, including humans.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1626642

Journal Information:: BMC Systems Biology, Journal Name: BMC Systems Biology Journal Issue: 1 Vol. 3; ISSN 1752-0509

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ 661 and proposing alternative drug targets Jamshidi, Neema; Palsson, Bernhard Ø BMC Systems Biology, Vol. 1, Issue 1 https://doi.org/10.1186/1752-0509-1-26	journal	June 2007
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Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli Schuetz, Robert; Kuepfer, Lars; Sauer, Uwe Molecular Systems Biology, Vol. 3, Issue 1 https://doi.org/10.1038/msb4100162	journal	January 2007
Metabolic control analysis in drug discovery and disease Cascante, Marta; Boros, Laszlo G.; Comin-Anduix, Begoña Nature Biotechnology, Vol. 20, Issue 3 https://doi.org/10.1038/nbt0302-243	journal	March 2002
A genome-scale, constraint-based approach to systems biology of human metabolism Mo, Monica L.; Jamshidi, Neema; Palsson, Bernhard Ø. Molecular BioSystems, Vol. 3, Issue 9 https://doi.org/10.1039/b705597h	journal	January 2007
Metabolic modelling of microbes: the flux-balance approach Edwards, Jeremy S.; Covert, Markus; Palsson, Bernhard Environmental Microbiology, Vol. 4, Issue 3 https://doi.org/10.1046/j.1462-2920.2002.00282.x	journal	March 2002
Global reconstruction of the human metabolic network based on genomic and bibliomic data Duarte, N. C.; Becker, S. A.; Jamshidi, N. Proceedings of the National Academy of Sciences, Vol. 104, Issue 6 https://doi.org/10.1073/pnas.0610772104	journal	January 2007
Bacteriophage-Specific Proteins in e. coli Infected with an rna Bacteriophage Nathans, D.; Oeschger, M. P.; Eggen, K. Proceedings of the National Academy of Sciences, Vol. 56, Issue 6 https://doi.org/10.1073/pnas.56.6.1844	journal	December 1966
Bayesian-based selection of metabolic objective functions Knorr, A. L.; Jain, R.; Srivastava, R. Bioinformatics, Vol. 23, Issue 3 https://doi.org/10.1093/bioinformatics/btl619	journal	December 2006
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Physical, Biochemical, and Immunological Properties of Coliphage MS-2 Particles Rohrmann, G. F.; Krueger, R. G. Journal of Virology, Vol. 6, Issue 3 https://doi.org/10.1128/JVI.6.3.269-279.1970	journal	January 1970
Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ 661 and proposing alternative drug targets Jamshidi, Neema; Palsson, Bernhard Ø BMC Systems Biology, Vol. 1, Issue 1 https://doi.org/10.1186/1752-0509-1-26	journal	June 2007
An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) Reed, Jennifer L.; Vo, Thuy D.; Schilling, Christophe H. Genome Biology, Vol. 4, Issue 9, p. R54 https://doi.org/10.1186/gb-2003-4-9-r54	journal	August 2003
Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli Schuetz, Robert; Kuepfer, Lars; Sauer, Uwe ETH Zurich https://doi.org/10.3929/ethz-b-000004128	text	January 2007

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Basic and applied uses of genome‐scale metabolic network reconstructions of Escherichia coli McCloskey, Douglas; Palsson, Bernhard Ø; Feist, Adam M. Molecular Systems Biology, Vol. 9, Issue 1 https://doi.org/10.1038/msb.2013.18	journal	January 2013
Nutrient limitation determines the fitness of cheaters in bacterial siderophore cooperation Sexton, D. Joseph; Schuster, Martin Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-00222-2	journal	August 2017
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59 BASIC BIOLOGICAL SCIENCES
flux balance analysis
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oxygen uptake rate
pentose phosphate pathway
uninfected cell

Title: Metabolic investigation of host/pathogen interaction using MS2-infected Escherichia coli

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