Cytolethal distending toxin (Cdt)-producing escherichia coli isolated from a child with bloody diarrhea in Japan

In a retrospective analysis by PCR, the cdtI gene encoding the cytolethal distending toxin (Cdt) was detected in Escherichia coli O2:H12 strain isolated from the bloody diarrheal stool specimen of a child. To our knowledge, this is the first report showing the possible association of Cdt-producing E. coli in Japan, particularly in a child with bloody diarrhea

An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli

Cytolethal distending toxins (CDTs) are inhibitory cyclomodulins, which block eukaryotic cell proliferation and are produced by a diverse group of Gram-negative bacteria, including Escherichia coli strains associated with intestinal and extraintestinal infections. However, the mode of transmission of the toxin gene clusters among diverse bacterial pathogens is unclear. We found that Cdt-I produced by enteropathogenic E. coli strains associated with diarrhea is encoded by a lambdoid prophage, which is inducible and infectious. The genome of Cdt-I converting phage (CDT-1Φ) comprises 47,021 nucleotides with 60 predicted ORFs organized into six genomic regions encoding the head and tail, virulence, integrase, unknown functions, regulation, and lysis. The genomic organization of CDT-1Φ is similar to those of SfV, a serotype-converting phage of Shigella flexneri, and UTI89, a prophage identified in uropathogenic E. coli. Besides the cdtI gene cluster, the virulence region of CDT-1Φ genome contains sequences homologous to a truncated cycle inhibiting factor and a type 3 effector protein. Mutation analysis of susceptible E. coli strain C600 suggested that the outer membrane protein OmpC is a putative receptor for CDT-1Φ. CDT-1Φ genome was also found to integrate into the host bacterial chromosome forming lysogens, which produced biologically active Cdt-I. Furthermore, phage induction appeared to cause enhanced toxigenicity of the E. coli strains carrying lysogenic CDT-1Φ. Our results suggest that CDT-1Φ is the latest member of a growing family of lambdoid phages encoding bacterial cyclomodulins and that the phage may have a role in horizontal transfer of these virulence genes

Cytolethal distending toxin A,B and C subunit proteins are necessary for the genotoxic effect of Escherichia Coli CDT-V

International audienceCytolethal distending toxins (CDT) are considered the prototype of inhibitory cyclomodulins, and are produced by a wide range of Gram-negative pathogenic bacteria, including Escherichia coli strains of various sero-and pathotypes. CDT is a heterotripartite toxin consisting of three protein subunits, CdtA, CdtB and CdtC. The active subunit, CdtB has DNase activity and causes DNA damage and cell cycle arrest in the target cell. However, several studies have highlighted different roles for CdtA and CdtC subunits. In order to reveal the necessity of CdtA and CdtC subunit proteins in the CDT-specific phenotype, expression clones containing the cdt-V subunit genes were constructed. Using cell culture assays, we demonstrated that clones expressing only the CdtB subunit or in combination with only CdtA or CdtC were unable to trigger the specific cell cycle arrest and changes in cell morphology in HeLa cells. At the same time, the recombinant clone harbouring the whole cdt-V operon caused all the CDT-associated characteristic phenotypes. All these results verify that all the three CDT subunit proteins are necessary for the genotoxic effect caused by CDT-V