The Bacterial Stress-Responsive Hsp90 Chaperone (HtpG) Is Required for the Production of the Genotoxin Colibactin and the Siderophore Yersiniabactin in Escherichia coli. (13th July 2016)

• Record Type: Journal Article
• Authors: Garcie, Christophe; Tronnet, Sophie; Garénaux, Amélie; McCarthy, Alex J.; Brachmann, Alexander O.; Pénary, Marie; Houle, Sébastien; Nougayrède, Jean-Philippe; Piel, Jörn; Taylor, Peter W.; Dozois, Charles M.; Genevaux, Pierre; Oswald, Eric; Martin, Patricia
• Is Part Of: Journal of infectious diseases. Volume 214:Number 6(2016:Sep. 15)
• Page Start: 916
• Page End: 924
• Publication Date: 2016-07-13
• Subjects: heat shock proteins -- Hsp90 -- HtpG -- stress response -- colibactin -- yersiniabactin -- siderophores -- virulence -- meningitis -- Escherichia coli; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiw294
• Languages: English
• ISSNs: 0022-1899

Abstract

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 (Hsp90 Ec ) 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 Hsp90 Ec are poorly known. Here, we demonstrated that production of colibactin and yersiniabactin is abolished in the absence of Hsp90 Ec . We further characterized an interplay between the Hsp90 Ec molecular chaperone and the ClpQ protease involved in colibactin and yersiniabactin synthesis. Finally, we demonstrated that Hsp90 Ec 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 Hps90 Ec in the production of two secondary metabolites involved in E. coli virulence.