The bully phage: A Shiga toxin-encoding prophage interferes with the induction of co-hosted prophages

Shiga toxin (Stx) prophages lysogenize various bacterial species, converting them into dangerous pathogens and driving the ongoing emergence of new outbreaks globally. These pathogens are polylysogens, harboring multiple prophages within their genomes. Yet, the impact of Stx prophage acquisition on resident prophages remains largely unknown. Using in vivo transmission studies with the murine pathogen Citrobacter rodentium that carries an Stx prophage, we demonstrate that the Stx prophage readily lysogenizes commensal Escherichia coli strains within the intestine. Markedly, this lysogenization altered the induction activity of prophages encoded within each new toxigenic host strain. Moreover, the Stx prophage abolished the induction of ϕNP, the most active native prophage of C. rodentium . We further show that ϕNP inhibition is mediated by the Stx Cro repressor, which exhibits dual functionality, promoting its own lytic cycle while repressing the expression of ϕNP lytic genes. Our findings reveal a novel competition strategy among prophages, and suggest that interfering with the induction of co-hosted prophages likely plays a role in the emergence and evolution of new Stx-producing pathogens.