Phage infection fronts trigger early sporulation and viral entrapment in bacterial populations.

Bacteriophages (phages) infect, lyse, and propagate within bacterial populations. However, physiological changes in bacterial cell state can protect against infection even within genetically susceptible populations. One such example is the generation of endospores by Bacillus and its relatives, characterized by a reversible state of reduced metabolic activity that protects cells against stressors including desiccation, energy limitation, antibiotics, and infection by phage. Here we tested how sporulation at the cellular scale impacts phage dynamics at population scales when propagating amongst B. subtilis in spatially structured environments. Plaques resulting from infection and lysis were approximately three-fold smaller on lawns of spore-forming bacteria vs. non-spore-forming bacteria. Analysis of plaque growth revealed that final plaque size was reduced due to an early termination of expanding phage plaques rather than the reduction of plaque growth speed. Microscopic imaging of the plaques revealed "sporulation rings," i.e. spores enriched around plaque edges relative to phage-free regions. We developed a series of mathematical models of phage, bacteria, spores, and small molecules that recapitulate plaque dynamics. We show evidence that phage infections trigger the formation of sporulation rings that reduce the productivity of phage infections and halt plaque spread even when resources are available for infection and lysis further away from plaque centers. Moreover, sporulation rings are also enriched in viable virospores, suggesting that although dormancy limits phage infections at population scales in the near term, viruses may co-opt phage-avoidance strategies to re-emerge over the long term, opening new avenues to explore the entangled fates of phages and their bacterial hosts.