Escherichia coli induces DNA double-strand breaks in eukaryotic cells

Science. 2006 Aug 11;313(5788):848-51. doi: 10.1126/science.1127059.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Death
  • Cell Line
  • Cell Nucleus / chemistry
  • Cytotoxins / metabolism*
  • DNA / analysis
  • DNA Damage*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / pathogenicity*
  • Escherichia coli / physiology*
  • G2 Phase
  • Genomic Islands*
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / microbiology
  • Molecular Sequence Data
  • Mutagenesis
  • Mutagens / metabolism*
  • Peptides / metabolism*
  • Phosphorylation
  • Polyketide Synthases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Cytotoxins
  • DNA-Binding Proteins
  • H2AX protein, human
  • Histones
  • Mutagens
  • Peptides
  • Tumor Suppressor Proteins
  • Polyketide Synthases
  • DNA
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AM229678