title: Host Characteristics and Bacterial Traits Predict Experimental Virulence for Escherichia coli Bloodstream Isolates From Patients With Urosepsis.
abstract: Background.  Extraintestinal Escherichia coli infections are common, costly, and potentially serious. A better understanding of their pathogenesis is needed. Methods.  Sixty-seven E coli bloodstream isolates from adults with urosepsis (Seattle, WA; 1980s) underwent extensive molecular characterization and virulence assessment in 2 infection models (murine subcutaneous sepsis and moth larval lethality). Statistical comparisons were made among host characteristics, bacterial traits, and experimental virulence. Results.  The 67 source patients were diverse for age, sex, and underlying medical and urological conditions. The corresponding E coli isolates exhibited diverse phylogenetic backgrounds and virulence profiles. Despite the E coli isolates' common bloodstream origin, they exhibited a broad range of experimental virulence in mice and moth larvae, in patterns that (for the murine model only) corresponded significantly with host characteristics and bacterial traits. The most highly mouse-lethal strains were enriched with classic "urovirulence" traits and typically were from younger women with anatomically and functionally normal urinary tracts. The 2 animal models corresponded poorly with one another. Conclusions.  Host compromise, including older age and urinary tract abnormalities, allows comparatively low-virulence E coli strains to cause urosepsis. Multiple E coli traits predict both experimental and epidemiological virulence. The larval lethality model cannot be a substitute for the murine sepsis model.
authors.affiliation: Veterans Affairs Medical Center ; Departments of Medicine.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Veterans Affairs Medical Center ; Departments of Medicine.
authors.forename: Stephen
authors.initials: S
authors.lastname: Porter
authors.affiliation: Veterans Affairs Medical Center ; Departments of Medicine.
authors.forename: Brian
authors.initials: B
authors.lastname: Johnston
authors.affiliation: Veterans Affairs Medical Center ; Psychiatry , University of Minnesota , Minneapolis.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuskowski
authors.affiliation: Swift Biosciences, Inc.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Spurbeck
authors.affiliation: Department of Microbiology , University of Michigan , Ann Arbor.
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
authors.affiliation: Department of Molecular Medicine and Pathology , University of Auckland , New Zealand.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Williamson
keywords: Escherichia coli infections; Galleria mellonella; host compromise; insect model; mouse model; phylogenetic group urosepsis; sepsis; virulence; virulence factors; virulence genes