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Sci Transl Med. 2017 Mar 22;9(382). pii: eaaf1283. doi: 10.1126/scitranslmed.aaf1283.

Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections.

Author information

1
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
2
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
3
Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
4
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
5
Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
6
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. livny@broadinstitute.org aearl@broadinstitute.org hultgren@wusm.wustl.edu.
7
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA. livny@broadinstitute.org aearl@broadinstitute.org hultgren@wusm.wustl.edu.
8
Center for Women's Infectious Disease Research, Washington University, St. Louis, MO 63110, USA.

Abstract

Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.

PMID:
28330863
PMCID:
PMC5653229
DOI:
10.1126/scitranslmed.aaf1283
[Indexed for MEDLINE]
Free PMC Article

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