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


RESULTS
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.


CONCLUSIONS
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.
Jain
Rishi
R
Department of Chemical, Materials and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA. jainr@ornl.gov
Srivastava
Ranjan
R
D001692:Biological Transport; D002952:Citric Acid Cycle; D019295:Computational Biology; D015536:Down-Regulation; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D016680:Genome, Bacterial / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D054884:Host-Pathogen Interactions; D017909:Levivirus / Q000502:physiology*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D015854:Up-Regulation
D005947:Glucose; D010100:Oxygen