Phage production is blocked in the adherent-invasive Escherichia coli LF82 upon macrophage infection

Adherent-invasive Escherichia coli (AIEC) strains are frequently recovered from stools of patients with dysbiotic microbiota. They have remarkable properties of adherence to the intestinal epithelium, and survive better than other E. coli in macrophages. The best studied of these AIEC is probably strain LF82, which was isolated from a Crohn’s disease patient. This strain contains five complete prophages, which have not been studied until now. We undertook their analysis, both in vitro and inside macrophages, and show that all of them form virions. The Gally prophage is by far the most active, generating spontaneously over 10(8) viral particles per mL of culture supernatants in vitro, more than 100-fold higher than the other phages. Gally is also over-induced after a genotoxic stress generated by ciprofloxacin and trimethoprim. However, upon macrophage infection, a genotoxic environment, this over-induction is not observed. Analysis of the transcriptome and key steps of its lytic cycle in macrophages suggests that the excision of the Gally prophage continues to be repressed in macrophages. We conclude that strain LF82 has evolved an efficient way to block the lytic cycle of its most active prophage upon macrophage infection, which may participate to its good survival in macrophages.