Viral commitment to infection depends on host metabolism

Viral infection begins with attachment to host surface structures such as receptors, pili, or porins. While prior research has focused on structural compatibility and recognition, the role of host physiology, particularly metabolic state, on viral commitment to infection remains underexplored. Here, we measured the adsorption rates (η) of five Escherichia coli phages representing various life cycles and entry pathways under controlled metabolic conditions. Four phages showed significantly reduced adsorption under energy-limited states, with weaker-binding phages being more sensitive. Using E. coli and its phages allowed us to institute a number of control infections that would be difficult with other organisms. Our findings support a two-step infection model where bound phages may disengage under unfavorable conditions, reducing commitment to non-productive infections. We observed a correlation between adsorption rates under energy-competent conditions and sensitivity to host metabolic state. Our results highlight host physiology as a key factor in virus–host interactions under energy-limited conditions.