Viral Infection Depends on Host’s Metabolism

Phage infection begins with physical interaction and host cell entry, occurring through various strategies including exploitation of surface receptors, pili, or porins. Research has predominantly emphasized structural compatibility between phage and host, particularly attachment and recognition mechanisms. However, one critical layer remains underexplored: how host physiological state, particularly metabolic activity, influences entry likelihood. Here, we quantitatively compared phage adsorption efficiencies across diverse Escherichia coli phages under controlled metabolic conditions. Using a standardized protocol, we measured adsorption rates ( η ) for five phages representing various life cycles (lytic, lysogenic, chronic) and entry pathways (LamB, FhuA, pilus, Tsx). Four of the five phages exhibited significantly reduced commitment to infection under energy-limited conditions. Notably, this effect varied. Phages with high baseline η were less sensitive to metabolic inhibition than phages with low baseline η . This observation suggests weak-binding phages may disengage under unfavorable conditions to avoid non-productive infections. Our findings support a twostep infection model, where host energy availability modulates the transition from reversible binding to irreversible commitment to infection. Our study highlights the importance of considering host physiology when studying virus-host dynamics, especially in energy-limited environments.