title: The Bacterial Stress-Responsive Hsp90 Chaperone (HtpG) Is Required for the Production of the Genotoxin Colibactin and the Siderophore Yersiniabactin in Escherichia coli.
abstract: The genotoxin colibactin, synthesized by Escherichia coli, is a secondary metabolite belonging to the chemical family of hybrid polyketide/nonribosomal peptide compounds. It is produced by a complex biosynthetic assembly line encoded by the pks pathogenicity island. The presence of this large cluster of genes in the E. coli genome is invariably associated with the high-pathogenicity island, encoding the siderophore yersiniabactin, which belongs to the same chemical family as colibactin. The E. coli heat shock protein HtpG (Hsp90Ec) is the bacterial homolog of the eukaryotic molecular chaperone Hsp90, which is involved in the protection of cellular proteins against a variety of environmental stresses. In contrast to eukaryotic Hsp90, the functions and client proteins of Hsp90Ec are poorly known. Here, we demonstrated that production of colibactin and yersiniabactin is abolished in the absence of Hsp90Ec We further characterized an interplay between the Hsp90Ec molecular chaperone and the ClpQ protease involved in colibactin and yersiniabactin synthesis. Finally, we demonstrated that Hsp90Ec is required for the full in vivo virulence of extraintestinal pathogenic E. coli This is the first report highlighting the role of heat shock protein Hps90Ec in the production of two secondary metabolites involved in E. coli virulence.
authors.affiliation: Service de Bactériologie-Hygiène, CHU Toulouse IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Christophe
authors.initials: C
authors.lastname: Garcie
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tronnet
authors.affiliation: Institut Armand Frappier, INRS, Laval, Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Garénaux
authors.affiliation: School of Pharmacy, University College London, United Kingdom.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCarthy
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule, Zurich, Switzerland.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Brachmann
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Marie
authors.initials: M
authors.lastname: Pénary
authors.affiliation: Institut Armand Frappier, INRS, Laval, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Houle
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Nougayrède
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule, Zurich, Switzerland.
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
authors.affiliation: School of Pharmacy, University College London, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
authors.affiliation: Institut Armand Frappier, INRS, Laval, Canada.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Dozois
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative, CNRS, Université Toulouse 3 Paul Sabatier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Genevaux
authors.affiliation: Service de Bactériologie-Hygiène, CHU Toulouse IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
authors.affiliation: Service de Bactériologie-Hygiène, CHU Toulouse IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049071:Endopeptidase Clp / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017208:Rats, Wistar; D017262:Siderophores / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; D018841:HSP90 Heat-Shock Proteins; C489352:HtpG protein, E coli; D009153:Mutagens; D010455:Peptides; D010636:Phenols; D061065:Polyketides; D017262:Siderophores; D013844:Thiazoles; C569566:colibactin; C104398:yersiniabactin; D049071:Endopeptidase Clp
keywords: Escherichia coli; Hsp90; HtpG; colibactin; heat shock proteins; meningitis; siderophores; stress response; virulence; yersiniabactin