Abstract

Urinary tract infections (UTIs) are one of the most common human bacterial infections. While UTIs are commonly associated with colonization by Escherichia coli, members of this species also have been found within the bladder of individuals with no lower urinary tract symptoms (no LUTS), also known as asymptomatic bacteriuria. Prior studies have found that both uropathogenic E. coli (UPEC) strains and E. coli isolates that are not associated with UTIs encode for virulence factors. Thus, the reason(s) why E. coli sometimes causes UTI-like symptoms remain(s) elusive. In this study, the genomes of 66 E. coli isolates from adult female bladders were sequenced. These isolates were collected from four cohorts, including women: (1) without lower urinary tract symptoms, (2) overactive bladder symptoms, (3) urgency urinary incontinence, and (4) a clinical diagnosis of UTI. Comparative genomic analyses were conducted, including core and accessory genome analyses, virulence and motility gene analyses, and antibiotic resistance prediction and testing. We found that the genomic content of these 66 E. coli isolates does not correspond with the participant’s symptom status. We thus looked beyond the E. coli genomes to the composition of the entire urobiome and found that the presence of E. coli alone was not sufficient to distinguish between the urobiomes of individuals with UTI and those with no LUTS. Because E. coli presence, abundance, and genomic content appear to be weak predictors of UTI status, we hypothesize that UTI symptoms associated with detection of E. coli are more likely the result of urobiome composition.

Highlights

  • Urinary tract infections (UTIs) affect about 150 million people per year, mounting large medical costs for individuals and communities (Flores-Mireles et al, 2015)

  • To evaluate the hypothesis that UTIs can be the result of colonization of the urinary tract by E. coli strains from the gut, we examined the genome annotations for the presence of 52 genes associated with flagellar synthesis, flagellar rotation, chemotactic signal transduction, and chemotactic membrane receptors

  • Because our results suggest that the E. coli genome itself does not correspond with UTI symptoms, we considered the E. coli isolates as a member of the bladder community

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Summary

Introduction

Urinary tract infections (UTIs) affect about 150 million people per year, mounting large medical costs for individuals and communities (Flores-Mireles et al, 2015). While several different bacterial species are known to cause UTIs, the most frequent culprit is uropathogenic E. coli (UPEC), which is thought to account for up to 74.4% of all community-acquired infections (Foxman, 2014). Phylogenomic studies have placed UPEC strains amongst multiple E. coli phylotypes (Moriel et al, 2016). Genome sequencing of UPEC isolates has identified numerous virulence factors and pathogenicity islands (Subashchandrabose and Mobley, 2015; Moriel et al, 2016; Terlizzi et al, 2017). There is evidence that the pathogenic potential of E. coli cannot be predicted from the presence of specific genetic content, such as a distinct virulence factor. UTI may be a result of multiple variables (Eto et al, 2007; Ragnarsdóttir et al, 2011; Brubaker and Wolfe, 2017; Schreiber et al, 2017)

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