Escherichia coli induces DNA double-strand breaks in eukaryotic cells.
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.
Nougayrède
Jean-Philippe
JP
INRA, UMR1225, Ecole Nationale Vétérinaire de Toulouse, Toulouse F-31076, France.
Homburg
Stefan
S
Taieb
Frédéric
F
Boury
Michèle
M
Brzuszkiewicz
Elzbieta
E
Gottschalk
Gerhard
G
Buchrieser
Carmen
C
Hacker
Jörg
J
Dobrindt
Ulrich
U
Oswald
Eric
E
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
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