title: A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites.
abstract: Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract.
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Wentong
authors.initials: W
authors.lastname: Cai
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Wannemuehler
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Dell'anna
authors.forename: Bryon
authors.initials: B
authors.lastname: Nicholson
authors.forename: Nicolle L
authors.initials: NL
authors.lastname: Barbieri
authors.forename: Subhashinie
authors.initials: S
authors.lastname: Kariyawasam
authors.forename: Yaping
authors.initials: Y
authors.lastname: Feng
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Logue
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Nolan
authors.forename: Ganwu
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D004927:Escherichia coli Infections / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D044404:Genomic Islands / Q000235:genetics; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism*; D051379:Mice; D011704:Pyelonephritis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D013045:Species Specificity; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D029968:Escherichia coli Proteins; D007656:Ketoglutaric Acids