Lytic bacteriophage have diverse indirect effects in a synthetic cross-feeding community

Bacteriophage shape the composition and function of microbial communities. Yet, it remains difficult to predict the effect of phage on microbial interactions. Specifically, little is known about how phage influence mutualisms in networks of cross-feeding bacteria. We modeled the impacts of phage in a synthetic microbial community in which Escherichia coli and Salmonella enterica exchange essential metabolites. In this model, phage attack of either species was sufficient to inhibit both members of the mutualism; however, the evolution of phage resistance ultimately allowed both species to attain yields similar to those observed in the absence of phage. In laboratory experiments, attack of S. enterica with P22 vir phage followed these modeling expectations of delayed community growth with little change in the final yield of bacteria. In contrast, when E. coli was attacked with T7 phage, S. enterica , the non-host species, reached higher yields compared to no-phage controls. T7 increased non-host yield by releasing consumable cell debris and by driving evolution of phage resistant E. coli that secreted more carbon. Additionally, E. coli evolved only partial resistance, increasing the total amount of lysed cells available for S. enterica to consume. Our results demonstrate that phage can have extensive indirect effects in microbial communities, and that the nature of these indirect effects depends on metabolic and evolutionary mechanisms.