title: Escherichia coli ClbS is a colibactin resistance protein.
abstract: The genomic pks island codes for the biosynthetic machinery that produces colibactin, a peptide-polyketide metabolite. Colibactin is a genotoxin that contributes to the virulence of extra-intestinal pathogenic Escherichia coli and promotes colorectal cancer. In this work, we examined whether the pks-encoded clbS gene of unknown function could participate in the self-protection of E. coli-producing colibactin. A clbS mutant was not impaired in the ability to inflict DNA damage in HeLa cells, but the bacteria activated the SOS response and ceased to replicate. This autotoxicity phenotype was markedly enhanced in a clbS uvrB double mutant inactivated for DNA repair by nucleotide excision but was suppressed in a clbS clbA double mutant unable to produce colibactin. In addition, ectopic expression of clbS protected infected HeLa cells from colibactin. Thus, ClbS is a resistance protein blocking the genotoxicity of colibactin both in the procaryotic and the eucaryotic cells.
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Bossuet-Greif
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.|CHU Toulouse, Service de bactériologie-Hygiène, Toulouse, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Dubois
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.|INP-ENVT ESC, Toulouse, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Petit
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tronnet
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.|CHU Toulouse, Service de bactériologie-Hygiène, Toulouse, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.affiliation: Université d'Auvergne, Inserm UMR 1071, INRA USC 2018, Clermont-Ferrand, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.|CHU Toulouse, Service de bactériologie-Hygiène, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
authors.affiliation: INRA, USC 1360, Toulouse, France.|Inserm, UMR 1043, Toulouse, France.|CNRS, UMR 5282, Toulouse, France.|Université de Toulouse, UPS, Toulouse, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Nougayrède
mesh_terms: D004249:DNA Damage; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000382:microbiology; D044404:Genomic Islands; D006367:HeLa Cells; D006801:Humans; D009153:Mutagens / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D014774:Virulence
chemical_list: D009153:Mutagens; D010455:Peptides; D061065:Polyketides; C569566:colibactin; D048630:Polyketide Synthases