Data highlighting phenotypic diversity of urine-associated Escherichia coli isolates.

This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see "Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities" [1].

Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities.

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.

Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in Uropathogenic Escherichia coli.

Two-component systems (TCSs) dictate many bacterial responses to environmental change via the activation of a membrane-embedded sensor kinase, which has molecular specificity for a cognate response regulator protein. However, although the majority of TCSs operate through seemingly strict cognate protein-protein interactions, there have been several reports of TCSs that violate this classical model of signal transduction. Our group has recently demonstrated that some of these cross-interacting TCSs function in a manner that imparts a fitness advantage to bacterial pathogens. In this study, we describe interconnectivity between the metabolite-sensing TCSs YpdA/YpdB and BtsS/BtsR in uropathogenic Escherichia coli (UPEC). The YpdA/YpdB and BtsS/BtsR TCSs have been previously reported to interact in K12 E. coli, where they alter the expression of putative transporter genes yhjX and yjiY, respectively. These target genes are both upregulated in UPEC during acute and chronic murine models of urinary tract infection, as well as in response to pyruvate and serine added to growth media in vitro. Here, we show that proper regulation of yhjX in UPEC requires the presence of all components from both of these TCSs. By utilizing plasmid-encoded luciferase reporters tracking the activity of the yhjX and yjiY promoters, we demonstrate that deletions in one TCS substantially alter transcriptional activity of the opposing system's target gene. However, unlike in K12 E. coli, single gene deletions in the YpdA/YpdB system do not alter yjiY gene expression in UPEC, suggesting that niche and lifestyle-specific pressures may be selecting for differential cross-regulation of TCSs in pathogenic and non-pathogenic E. coli.