Thinking Phage Innovations Through Evolution and Ecology

In this article, we conduct an interdisciplinary review of the potential of phage-based applications in light of current knowledge about phage evolution and ecology. Gaining an improved understanding of phages' ecology and evolutionary dynamics is crucial for recognizing both the benefits and limits of their usage, as well as potential negative downstream effects across different ecological milieus. As a reference, the history of the industrialization of antibiotics and the rise of antimicrobial resistance act as a reminder of the deep entanglement of both the evolvability capacities of micro-organisms and the history of human societies. Based on evolutionary biological parameters, we show that (1) virulent bacteriophages are best candidates for biocontrol, (2) best cocktails harbor complementary bacteriophages preventing bacterial cross-resistance, and (3) cure can also be considered with steer of bacterial bacteriophage-resistance evolution toward loss of virulence factor and/or increase in antibiotic susceptibility. A detailed review of what is known about the role of phages in vine cultivation and wine production finally serves as an example to show how it is important to consider site-specific rather than one-size-fits-all responses.