Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology.
Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins.
Department Cell and Molecular Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden. francesca.grasso@ki.se.
Francesca
F
Grasso
Department Cell and Molecular Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Teresa.Frisan@ki.se.
Teresa
T
Frisan
D000818:Animals; D001424:Bacterial Infections / Q000235:genetics*; D001427:Bacterial Toxins / Q000737:chemistry / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*
D001427:Bacterial Toxins; D009153:Mutagens
DNA damage response; bacterial genotoxins; cancer; chronic infection; probiotics