title: Escherichia coli induces DNA double-strand breaks in eukaryotic cells.
abstract: Transient infection of eukaryotic cells with commensal and extraintestinal pathogenic Escherichia coli of phylogenetic group B2 blocks mitosis and induces megalocytosis. This trait is linked to a widely spread genomic island that encodes giant modular nonribosomal peptide and polyketide synthases. Contact with E. coli expressing this gene cluster causes DNA double-strand breaks and activation of the DNA damage checkpoint pathway, leading to cell cycle arrest and eventually to cell death. Discovery of hybrid peptide-polyketide genotoxins in E. coli will change our view on pathogenesis and commensalism and open new biotechnological applications.
authors.affiliation: INRA, UMR1225, Ecole Nationale Vétérinaire de Toulouse, Toulouse F-31076, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Nougayrède
authors.forename: Stefan
authors.initials: S
authors.lastname: Homburg
authors.forename: Frédéric
authors.initials: F
authors.lastname: Taieb
authors.forename: Michèle
authors.initials: M
authors.lastname: Boury
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Brzuszkiewicz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gottschalk
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
authors.forename: Jörg
authors.initials: J
authors.lastname: Hacker
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dobrindt
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003603:Cytotoxins / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D016195:G2 Phase; D044404:Genomic Islands; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D048630:Polyketide Synthases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D003603:Cytotoxins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009153:Mutagens; D010455:Peptides; D025521:Tumor Suppressor Proteins; D048630:Polyketide Synthases; D004247:DNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases