TY - JOUR
T1 - Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli
T2 - The Status of the Field and New Clinical Opportunities
AU - Eberly, Allison R.
AU - Beebout, Connor J.
AU - Carmen Tong, Ching Man
AU - Van Horn, Gerald T.
AU - Green, Hamilton D.
AU - Fitzgerald, Madison J.
AU - De, Shuvro
AU - Apple, Emily K.
AU - Schrimpe-Rutledge, Alexandra C.
AU - Codreanu, Simona G.
AU - Sherrod, Stacy D.
AU - McLean, John A.
AU - Clayton, Douglass B.
AU - Stratton, Charles W.
AU - Schmitz, Jonathan E.
AU - Hadjifrangiskou, Maria
N1 - Publisher Copyright:
© 2019
PY - 2020/2/14
Y1 - 2020/2/14
N2 - Urinary tract infections (UTIs) represent a major burden across the population, although key facets of their pathophysiology and host interaction remain unclear. Escherichia coli epitomizes these obstacles: this gram-negative bacterial species is the most prevalent agent of UTIs worldwide and can also colonize the urogenital tract in a phenomenon known as asymptomatic bacteriuria (ASB). Unfortunately, at the level of the individual E. coli strains, the relationship between UTI and ASB is poorly defined, confounding our understanding of microbial pathogenesis and strategies for clinical management. Unlike diarrheagenic pathotypes of E. coli, the definition of uropathogenic E. coli (UPEC) remains phenomenologic, without conserved phenotypes and known genetic determinants that rigorously distinguish UTI- and ASB-associated strains. This article provides a cross-disciplinary review of the current issues from interrelated mechanistic and diagnostic perspectives and describes new opportunities by which clinical resources can be leveraged to overcome molecular challenges. Specifically, we present our work harnessing a large collection of patient-derived isolates to identify features that do (and do not) distinguish UTI- from ASB-associated E. coli strains. Analyses of biofilm formation, previously reported to be higher in ASB strains, revealed extensive phenotypic heterogeneity that did not correlate with symptomatology. However, metabolomic experiments revealed distinct signatures between ASB and cystitis isolates, including in the purine pathway (previously shown to be critical for intracellular survival during acute infection). Together, these studies demonstrate how large-scale, wild-type approaches can help dissect the physiology of colonization versus infection, suggesting that the molecular definition of UPEC may rest at the level of global bacterial metabolism.
AB - Urinary tract infections (UTIs) represent a major burden across the population, although key facets of their pathophysiology and host interaction remain unclear. Escherichia coli epitomizes these obstacles: this gram-negative bacterial species is the most prevalent agent of UTIs worldwide and can also colonize the urogenital tract in a phenomenon known as asymptomatic bacteriuria (ASB). Unfortunately, at the level of the individual E. coli strains, the relationship between UTI and ASB is poorly defined, confounding our understanding of microbial pathogenesis and strategies for clinical management. Unlike diarrheagenic pathotypes of E. coli, the definition of uropathogenic E. coli (UPEC) remains phenomenologic, without conserved phenotypes and known genetic determinants that rigorously distinguish UTI- and ASB-associated strains. This article provides a cross-disciplinary review of the current issues from interrelated mechanistic and diagnostic perspectives and describes new opportunities by which clinical resources can be leveraged to overcome molecular challenges. Specifically, we present our work harnessing a large collection of patient-derived isolates to identify features that do (and do not) distinguish UTI- from ASB-associated E. coli strains. Analyses of biofilm formation, previously reported to be higher in ASB strains, revealed extensive phenotypic heterogeneity that did not correlate with symptomatology. However, metabolomic experiments revealed distinct signatures between ASB and cystitis isolates, including in the purine pathway (previously shown to be critical for intracellular survival during acute infection). Together, these studies demonstrate how large-scale, wild-type approaches can help dissect the physiology of colonization versus infection, suggesting that the molecular definition of UPEC may rest at the level of global bacterial metabolism.
KW - Asymptomatic bacteriuria
KW - Cystitis
KW - Metabolomics
KW - Urinary tract infection
KW - Uropathogenic Escherichia coli
UR - http://www.scopus.com/inward/record.url?scp=85076825439&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2019.11.008
DO - 10.1016/j.jmb.2019.11.008
M3 - Article
C2 - 31794727
AN - SCOPUS:85076825439
SN - 0022-2836
VL - 432
SP - 786
EP - 804
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 4
ER -