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

Abstract

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 P22vir 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.

Phage cocktail strategies for the suppression of a pathogen in a cross-feeding coculture

“…To start, we modified a 201 resource-explicit model of the coculture that simulated the abundance of bacteria, phage, and 202 resources through time (Fig 4a) (Fazzino et al, 2020). We used model parameters informed by 203 literature values and used wet-lab experiments to measure maximum growth rates (Table S2, 204 Fig 4b), and confirmed that the model accurately simulated the growth dynamics of the phage-205 free coculture (Fig 4c) (Fazzino et al, 2020). Phage-resistant bacteria were seeded in at low 206 frequencies to approximate standing variation for phage resistance.…”

“…To represent our cross-feeding microbial community, we modified a series of resource-explicit 403 ordinary differential equations to simulate an E. coli and S. enterica cross-feeding system in 404 which one species grows on nutrients secreted by the other (Fazzino et al, 2020). We used 405…”

“…Lactose is seeded in and is depleted as Table 421 S2) (Fazzino et al, 2020). Bacterial growth rates were measured from wet-lab monoculture 422 experiments (E. coli grown in lactose + methionine and S. enterica grown in acetate) where 423 OD600 was measured every 20min.…”

The Power of Metabolism for Predicting Microbial Community Dynamics

“…Instead, we saw an increase in abundance of metabolically dependent S. enterica (11). A closer examination revealed a metabolic explanation: phage lysis released nutrients in the environment which the metabolic partner could then scavenge, reminiscent of the “viral shunt” which cycles nutrients in marine food webs (12).…”

Cross-feeding modulates the rate and mechanism of antibiotic resistance evolution in a model microbial community of Escherichia coli and Salmonella enterica

“…Sequence analysis was performed using BreSeq (48) to align Illumina reads to reference E. coli and S. enterica genomes as previously described (49). Briefly, mutation lists for resistant populations were filtered such that variation between our ancestral strains and the reference genome were removed, as well as any mutations which also arose in the antibiotic-free populations.…”