Tóth I, Nougayrède JP, Dobrindt U, Ledger TN, Boury M, Morabito S, Fujiwara T, Sugai M, Hacker J, Oswald E (2008): Type I and type IV cytolethal distending toxin genes are framed with lambdoid prophage genes in extraintestinal pathogenic Escherichia coli
Infect. Immun.: 2008 Nov 3. [Epub ahead of print].

Five types of cytolethal distending toxin (CDT- I to V) have been identified in Escherichia coli. In the present study we have cloned and sequenced the cdt-IV operon and flanking region from a porcine extraintestinal pathogenic E. coli (ExPEC) strain of the serogroup O75. We confirmed that similar to other CDTs, CDT-IV induced phosphorylation of host histone H2AX, a sensitive marker of DNA double strand breaks, and blocked HeLa cell cycle at the G₂/M transition. The cdt-IV genes were framed by lambdoid prophage genes. We cloned and sequenced the cdt-I operon and flanking regions from a human O18:K1:H7 ExPEC strain and observed that cdt-I genes were also flanked by lambdoid prophage genes. PCR studies indicated that a gene coding for a putative protease was always associated with the cdtC-IV gene, but was not associated to cdtC genes in strains producing CDT-I, III, and V. Our results suggest that cdt-I and cdt-IV genes might have been acquired from a common ancestor by phage transduction and evolved in their bacterial hosts. These lysogenic bacteriophages have the potential to carry non-essential "cargo" genes or "morons" and therefore play a crucial role in the generation of genetic diversity within ExPEC.