Bacterial virulence phenotypes ofEscherichia coliand host susceptibility determine risk for urinary tract infections.
Urinary tract infections (UTIs) are caused by uropathogenicEscherichia coli(UPEC) strains. In contrast to many entericE. colipathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study usingE. coliisolates 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, theE. colistrain 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.
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Henry L
0000-0002-4501-9886
HL
Schreiber
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
Matt S
0000-0001-6834-6831
MS
Conover
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Wen-Chi
0000-0001-8408-3533
WC
Chou
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
Michael E
0000-0002-0072-6210
ME
Hibbing
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Abigail L
0000-0002-3800-0714
AL
Manson
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
Karen W
KW
Dodson
Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
Thomas J
0000-0003-0498-8231
TJ
Hannan
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Pacita L
PL
Roberts
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Ann E
0000-0003-0130-8659
AE
Stapleton
Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Thomas M
0000-0001-5810-6543
TM
Hooton
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. livny@broadinstitute.org aearl@broadinstitute.org hultgren@wusm.wustl.edu.
Jonathan
0000-0001-6589-3020
J
Livny
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. livny@broadinstitute.org aearl@broadinstitute.org hultgren@wusm.wustl.edu.
Ashlee M
0000-0001-7857-9145
AM
Earl
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA. livny@broadinstitute.org aearl@broadinstitute.org hultgren@wusm.wustl.edu.|Center for Women's Infectious Disease Research, Washington University, St. Louis, MO 63110, USA.
Scott J
0000-0001-8785-564X
SJ
Hultgren
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D060085:Coinfection / Q000382:microbiology; D015169:Colony Count, Microbial; D003556:Cystitis / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D010802:Phylogeny; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000382:microbiology*; D014556:Urine / Q000382:microbiology; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000378:metabolism
D015415:Biomarkers; D037521:Virulence Factors