title: The Enterobacterial Genotoxins: Cytolethal Distending Toxin and Colibactin.
abstract: While the DNA damage induced by ionizing radiation and by many chemical compounds and drugs is well characterized, the genotoxic insults inflicted by bacteria are only scarcely documented. However, accumulating evidence indicates that we are exposed to bacterial genotoxins. The prototypes of such bacterial genotoxins are the Cytolethal Distending Toxins (CDTs) produced by Escherichia coli and Salmonella enterica serovar Typhi. CDTs display the DNase structure fold and activity, and induce DNA strand breaks in the intoxicated host cell nuclei. E. coli and certain other Enterobacteriaceae species synthesize another genotoxin, colibactin. Colibactin is a secondary metabolite, a hybrid polyketide/nonribosomal peptide compound synthesized by a complex biosynthetic machinery. In this review, we summarize the current knowledge on CDT and colibactin produced by E. coli and/or Salmonella Typhi. We describe their prevalence, genetic determinants, modes of action, and impact in infectious diseases or gut colonization, and discuss the possible involvement of these genotoxigenic bacteria in cancer.
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), INRA UMR1416, INSERM U1220, Université de Toulouse, CHU Purpan, Toulouse, FRANCE.
authors.forename: Frederic
authors.initials: F
authors.lastname: Taieb
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), INRA UMR1416, INSERM U1220, Université de Toulouse, CHU Purpan, Toulouse, FRANCE.
authors.forename: Claude
authors.initials: C
authors.lastname: Petit
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), INRA UMR1416, INSERM U1220, Université de Toulouse, CHU Purpan, Toulouse, FRANCE.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Nougayrède
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), INRA UMR1416, INSERM U1220, Université de Toulouse, CHU Purpan, Toulouse, FRANCE.
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D004249:DNA Damage; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D051379:Mice; D009153:Mutagens; D009369:Neoplasms / Q000382:microbiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D012485:Salmonella typhi / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D001427:Bacterial Toxins; D009153:Mutagens; D010455:Peptides; D061065:Polyketides; C569566:colibactin; C067044:cytolethal distending toxin