Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 219, Issue 1, Pages 121-132Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy459
Keywords
Escherichia coli; virulence; sepsis; mouse models; phylogenetic groups; virulence factors; sequence types; clinical isolates; fecal isolates
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Funding
- Office of Research and Development, Department of Veterans Affairs [1 I01 CX000920-01, 2I01CX000920-04]
- National Institutes of Health [R21AI117654]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI117654] Funding Source: NIH RePORTER
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Background. The distinguishing characteristics of extraintestinal pathogenic Escherichia coli (ExPEC) strains are incompletely defined. Methods. We characterized 292 diverse-source human Escherichia coli isolates (116 from fecal specimens, 79 from urine specimens [of which 39 were from patients with cystitis and 40 were from patients with pyelonephritis], and 97 from blood specimens) for phylogenetic group, sequence type complex (STc), and 49 putative extraintestinal pathogenic E. coli (ExPEC)-associated virulence genes. We then assessed these traits and ecological source as predictors of illness severity in a murine sepsis model. Results. The study isolates exhibited a broad range of virulence in mice. Most of the studied bacterial characteristics corresponded significantly with experimental virulence, as did ecological source and established molecular definitions of ExPEC and uropathogenic E. coli (UPEC). Multivariable modeling identified the following bacterial traits as independent predictors of illness severity both overall and among the fecal and clinical (ie, urine and blood) isolates separately: fyuA (yersiniabactin receptor), kpsM K1 (K1 capsule), and kpsM II (group 2 capsules). Molecular UPEC status predicted virulence independently only among fecal isolates. Neither ecological source (ie, clinical vs fecal) nor molecular ExPEC status added predictive power to these traits, which accounted collectively for up to 49% of the observed variation in virulence. Conclusions. Among human-source E. coli isolates, specific accessory traits and phylogenetic/clonal backgrounds predict experimental virulence in a murine sepsis model better than does ecological source.
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