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Updated: Apr 3, 2026

Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
Synergy and antagonism in a genome-scale model of metabolic hijacking by bacteriophages
Jordan C Rozum1, William Sineath1,2, Pavlo Bohutskyi1
1Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Abstract:
Bacteriophage auxiliary metabolic genes (AMGs) alter host metabolism by hijacking reactions, but previous studies mostly inferred their roles from annotations, ignoring system-wide impacts and phage production. Here we integrate AMGs and phage assembly into a genome-scale metabolic model of Prochloroccocus marinus MED4 infected by P-HM2. We show that 17 directly hijacked reactions substantially affect more than 30% of the reactions in MED4 metabolism, including carbon fixation, photosynthesis, and nucleotide synthesis, distinguishing these AMGs as either phage aligned-shifting feasible reaction velocities in accordance with maximal phage production-or phage antialigned. Pareto optimization reveals that phage-aligned reactions alter phage-host growth trade-offs, while phage-antialigned reactions do not. We experimentally validate our predictions of system-level AMG impacts by measuring the N-dependent effect of P-HM2 cp12 expression on growth in a model relative of the genetically intractable MED4, Synechococcus elongatus. We also show that AMGs' indirect impacts are synergistically and antagonistically coupled, providing systems-level insight into AMG perturbations and highlighting how nontrivial cascading effects shape host metabolism.
Insights
Bacteriophage auxiliary metabolic genes (AMGs) hijack host metabolism, impacting over 30% of reactions. Some AMGs optimize phage production, revealing system-level effects on host-phage interactions.
Area of Science:
- Microbiology
- Metabolic Engineering
- Systems Biology
Background:
- Bacteriophage auxiliary metabolic genes (AMGs) modify host metabolism.
- Previous studies inferred AMG roles from annotations, overlooking system-wide impacts and phage production.
Purpose of the Study:
- To integrate AMGs and phage assembly into a genome-scale metabolic model.
- To analyze system-wide impacts of AMGs on host metabolism and phage production.
Main Methods:
- Developed a genome-scale metabolic model for *Prochloroccocus marinus* MED4 infected by P-HM2.
- Integrated AMGs and phage assembly into the model.
- Utilized Pareto optimization to analyze phage-aligned and anti-aligned reactions.
- Experimentally validated predictions using *Synechococcus elongatus*.
Main Results:
- 17 hijacked reactions affect over 30% of MED4 metabolism, including carbon fixation and photosynthesis.
- Phage-aligned AMGs alter host-phage growth trade-offs, while phage-anti-aligned AMGs do not.
- AMGs exhibit synergistic and antagonistic indirect impacts on host metabolism.
Conclusions:
- AMGs cause substantial system-level perturbations in host metabolism.
- Understanding AMG impacts is crucial for predicting phage-host dynamics and cascading effects.
- This study provides systems-level insights into AMG functions and their metabolic consequences.
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