The Bacterial Stress-Responsive Hsp90 Chaperone (HtpG) Is Required for the Production of the Genotoxin Colibactin and the Siderophore Yersiniabactin in Escherichia coli

J Infect Dis. 2016 Sep 15;214(6):916-24. doi: 10.1093/infdis/jiw294. Epub 2016 Jul 13.


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.

Keywords: Escherichia coli; Hsp90; HtpG; colibactin; heat shock proteins; meningitis; siderophores; stress response; virulence; yersiniabactin.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endopeptidase Clp / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Female
  • Gene Deletion
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mutagens / metabolism*
  • Peptides / metabolism*
  • Phenols / metabolism*
  • Polyketides / metabolism*
  • Protein Interaction Mapping
  • Rats, Wistar
  • Siderophores / metabolism*
  • Thiazoles / metabolism*
  • Virulence


  • Escherichia coli Proteins
  • HSP90 Heat-Shock Proteins
  • HtpG protein, E coli
  • Mutagens
  • Peptides
  • Phenols
  • Polyketides
  • Siderophores
  • Thiazoles
  • colibactin
  • yersiniabactin
  • Endopeptidase Clp