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