Bacteriophage Transcription Factor Cro Regulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli

Juan D. Hernandez-Doria, Vanessa Sperandio

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Bacteriophage-encoded genetic elements control bacterial biological functions. Enterohemorrhagic Escherichia coli (EHEC) strains harbor lambda-phages encoding the Shiga-toxin (Stx), which is expressed during the phage lytic cycle and associated with exacerbated disease. Phages also reside dormant within bacterial chromosomes through their lysogenic cycle, but how this impacts EHEC virulence remains unknown. We find that during lysogeny the phage transcription factor Cro activates the EHEC type III secretion system (T3SS). EHEC lambdoid phages are lysogenic under anaerobic conditions when Cro binds to and activates the promoters of T3SS genes. Interestingly, the Cro sequence varies among phages carried by different EHEC outbreak strains, and these changes affect Cro-dependent T3SS regulation. Additionally, infecting mice with the related pathogen C. rodentium harboring the bacteriophage cro from EHEC results in greater T3SS gene expression and enhanced virulence. Collectively, these findings reveal the role of phages in impacting EHEC virulence and their potential to affect outbreak strains. Hernandez-Doria and Sperandio demonstrated that enterohemorrhagic Escherichia coli (EHEC) associates with bacteriophages, which reside dormant (lysogeny) under anaerobic conditions. While lysogenic, bacteriophages produce a protein, Cro, that either activates or represses virulence factors among different EHEC strains and thus could impact EHEC virulence during outbreaks.

Original languageEnglish (US)
Pages (from-to)607-617.e6
JournalCell Host and Microbe
Issue number5
StatePublished - May 9 2018


  • Shiga toxin
  • bacteriophage
  • enterohemorrhagic E. coli (EHEC)
  • gene regulation
  • locus of enterocyte effacement (LEE)
  • pathogenicity islands

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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