Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells.
Escherichia coli is a normal inhabitant of the human gut. However, E. coli strains of phylogenetic group B2 harbor a genomic island called "pks" that codes for the production of a polyketide-peptide genotoxin, Colibactin. Here we report that in vivo infection with E. coli harboring the pks island, but not with a pks isogenic mutant, induced the formation of phosphorylated H2AX foci in mouse enterocytes. We show that a single, short exposure of cultured mammalian epithelial cells to live pks(+) E. coli at low infectious doses induced a transient DNA damage response followed by cell division with signs of incomplete DNA repair, leading to anaphase bridges and chromosome aberrations. Micronuclei, aneuploidy, ring chromosomes, and anaphase bridges persisted in dividing cells up to 21 d after infection, indicating occurrence of breakage-fusion-bridge cycles and chromosomal instability. Exposed cells exhibited a significant increase in gene mutation frequency and anchorage-independent colony formation, demonstrating the infection mutagenic and transforming potential. Therefore, colon colonization with these E. coli strains harboring the pks island could contribute to the development of sporadic colorectal cancer.
Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1225, F-31076 Toulouse, France.
Gabriel
G
Cuevas-Ramos
Claude R
CR
Petit
Ingrid
I
Marcq
Michèle
M
Boury
Eric
E
Oswald
Jean-Philippe
JP
Nougayrède
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009153:Mutagens / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism
D009153:Mutagens