title: Uropathogenic Escherichia coli use d-serine deaminase to modulate infection of the murine urinary tract.
abstract: Although once thought to be unique to bacteria, d-amino acids are also produced by mammals. For example, d-serine is excreted in human urine at concentrations ranging from 3.0 to 40 micro g ml-1. An epidemiological survey demonstrated that urine isolates of E. coli are more likely to catabolise d-serine via expression of d-serine deaminase, DsdA than enteric disease isolates. The urosepsis strain, CFT073, and an isogenic dsdA mutant have similar growth kinetics in minimal or complex media. However, relative to the wild type, the dsdA mutant has a pleiomorphic cell shape and a prolonged, 4-6 h lag phase when grown in human urine. This suggests that d-serine catabolism provides a growth advantage in the urinary tract. Unexpectedly, in a direct competition model of urinary tract infection, the dsdA mutant was recovered 300-times more frequently than the wild type in the bladders of mice 48 h after infection. A new model of E. coli uropathogenesis is proposed where growth and gene expression are modulated in response to environmental d-serine levels. In support of this, the CFT073 dsdA mutant is hyperflagellated and more motile than the wild type indicating that intracellular levels of d-serine may directly or indirectly influence the expression of regulons associated with E. coli uropathogenesis.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine, 1300 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Roesch
authors.forename: Peter
authors.initials: P
authors.lastname: Redford
authors.forename: Stephanie
authors.initials: S
authors.lastname: Batchelet
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Moritz
authors.forename: Shahaireen
authors.initials: S
authors.lastname: Pellett
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Haugen
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Blattner
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Welch
mesh_terms: D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D048429:Cell Size; D004926:Escherichia coli / Q000166:cytology / Q000201:enzymology* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012694:Serine / Q000378:metabolism; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000382:microbiology*; D014556:Urine / Q000382:microbiology; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D037521:Virulence Factors; D012694:Serine; D006836:Hydro-Lyases; C101950:D-serine dehydratase