Probiotic phage steering of disease suppressive rhizosphere microbiome

ABSTRACT Current phage therapy approaches predominantly focus on targeting pathogenic bacteria, overlooking the vast potential of phages that interact with beneficial, plant growth-promoting (probiotic) bacteria. Here we tested if a single phage targeting a probiotic Stenotrophomonas maltophilia bacterium can steer the rhizosphere microbiome disease suppressiveness against Ralstonia solanacearum phytopathogen. We find that S. maltophilia quickly evolves resistance to its phage via mutations in ssb and TonB genes and by upregulating anti-phage defense systems. Crucially, evolution of phage resistance reprograms the bacterial transcriptome and metabolome, leading to unexpectedly enhanced antimicrobial activity against the R. solanacearum . Furthermore, exposing S. maltophilia to phage in the tomato rhizosphere increases the microbiota-wide disease suppressiveness by stabilizing bacterial diversity and facilitating pathogen suppression by other resident species. Our findings suggest that probiotic-specific phages could be used as ecological and evolutionary engineers to steer the rhizosphere microbiome disease suppressiveness through activation of antagonistic bacterial interactions.