From Decision to Destruction: A Unified Framework of Molecular Strategies Governing Bacteriophage Lytic Biology

Existing studies in bacteriophage biology have largely examined individual components of the phage life cycle alone. These include lysis mechanisms, depolymerases, and developmental pathways. However, successful phage infection depends on the coordinated progression of interconnected events, from developmental commitment to host cell lysis. In this review, we present a systems-level perspective that views the phage lytic cycle as an integrated infection program rather than a collection of independent events. We examine the functional links between environmental sensing, lysis–lysogeny decision-making, population-level communication, host recognition, surface penetration, and terminal lysis, highlighting how each stage influences the next. Understanding these connections is increasingly important for phage engineering and synthetic biology, as a fragmented view can limit the rational design of engineered phages and phage-derived tools. By identifying these molecular nuances that govern productive infection, this review reveals opportunities to develop improved phage-derived enzymes, programmable lysis systems, and next-generation antibacterial therapeutics.