Making waves: Intelligent phage cocktail design, a pathway to precise microbial control in water systems.

Current practices in water and wastewater treatment to control unwanted microbes have led to new problems, including health effects from disinfection byproducts, growth of opportunistic pathogens resistant to residual disinfectants (e.g., chlorine), and antibiotic resistance. These challenges are spurring interest in rethinking our practices of microbial control. Simultaneously, advances in molecular biology and computation power are driving renewed interest in using phages (viruses that infect bacteria) to precisely control microbial growth (aka, phage biocontrol). In this Making Waves article, I begin by reviewing the current state of research into phage cocktail design, emphasizing our limited understanding of the features of successful phage cocktails (combinations of multiple types of phages). I describe the state of modeling phage-bacteria interactions and underscore the need for increasing research efforts to predict phage cocktail success, a key gap slowing the application of phage biocontrol. I also detail how research must also focus on techniques for engineering more effective phages to offer a more rapid alternative to phage discovery from natural environments. In this way, phage cocktails comprised of phages with complementary infection strategies may be designed. The final area for increased research effort that I highlight is the need for phage cocktail design to account for possible unintended environmental effects, a risk that is increasingly acknowledged in phage ecology studies but mostly ignored by those developing phage biocontrol technologies. By focusing more research effort towards the areas necessary for intelligent phage cocktail design, we can accelerate the development of phage-based biocontrol in water systems and improve public health.