How many ways are there to be a phage?

Rachel Szabo , Martin Ackermann

The search for predictive rules for how microbiomes assemble and function rarely include their most abundant members: phages. Nearly a century of phage research has yielded few ecological principles for the impacts of phages within microbial communities – sequencing surveys resolve phage presence but not phage activity, while mechanistic studies of relatively few model phages provide insights that are deep but narrow. The same challenge of connecting observations between complex communities and diverse individuals also exists in bacterial ecology, where this gap is being bridged by coarse-graining species into functional groups defined by their metabolic activities. Phages, having no metabolism of their own, require a different approach. Here, we argue for building a quantitative, trait-based framework for phage ecology based on the life history traits that determine their reproduction and survival. Creating such a framework has become possible only now due to recent advances that make high-throughput phage phenotyping feasible at an unprecedented scale. We propose that an extensive, systematic map of phage trait space has the potential to reveal phage functional groups arising from physiological or evolutionary trade-offs. Because phage traits are not fixed properties across conditions, this map must contain functions describing the dependence of phage traits on host physiology and the chemical environment. Comparing these functions across phages can generate testable predictions about which phage types succeed, coexist, or exclude one another across conditions and can provide a basis for linking complex virome compositions to the ecological processes that shape them. Ultimately, ecological frameworks for phages would improve models of microbiome dynamics, unlock greater interpretability of phage sequence data, and support the rational design of phage-based microbiome interventions.