Nutrient Uptake Shifts During T4 Phage Replication in Escherichia coli

Abstract

The rising threat of antibiotic resistance has prompted renewed interest in alternative therapies, such as phage therapy. Phage therapy offers a targeted approach by lysing specific bacterial hosts, potentially circumventing antibiotic resistance. Our study investigates the host-pathogen interaction between Escherichia coli and T4 bacteriophage, a virus that targets only E. coli, with a focus on metabolic changes during infection. E. coli relies on various carbon sources to fuel its metabolic pathways, and viral infection can reprogram host metabolism to prioritize viral replication, often depleting cellular energy and nucleotide pools. Previous studies on other viruses have shown variable dependence on nutrients such as glucose and glutamine for replication. To determine nutrient utilization by T4 phage, uptake assays adapted for bacterial cells were conducted to examine glucose and glutamine consumption in uninfected versus phage-infected E. coli cells. Infected cells showed a marked increase in uptake of both glucose and glutamine, suggesting that both are critical for efficient viral replication. Ongoing research using glutaminase and glutamine synthetase knockout strains will help clarify the specific roles of these pathways in supporting phage propagation.