Genomic Survey of E. coli From the Bladders of Women With and Without Lower Urinary Tract Symptoms

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.

Long-term stability of the urogenital microbiota of asymptomatic European women

“…The protective role of particular strains belonging to Lactobacillus jensenii [24,25], can possibly contribute to the health maintenance of an individual with high abundance of Enterobacteriaceae, including an uropathogenic ST131 Escherichia coli (UPEC) according to its gene content [26] (unpublished data). This data also highlights the relevance of strain level characterization to understand FUM role in health and disease, as previously noticed [27,28].…”

Gut-bladder axis syndrome associated with recurrent UTIs in humans

“…Mapping urine metagenome assemblies to a curated virulence factor database showed that UTI-causing strains were enriched in virulence factors (including iron uptake systems ( sit, chu, iro, ybt operons), colibactin ( clb ), and type 6 secretion systems) relative to an E. coli species-wide database, though many of these were also present in the one urine sample from a control participant for which we had sufficient coverage to assess gene content ( Methods , Table S8). This apparent transition of a likely urovirulent strain to the bladder of healthy women without eliciting UTI symptoms is consistent with previous studies which have been unable to identify genetic markers of urovirulence in mice 48 , or consistently discriminate between UTI and asymptomatic bacteriuria strains in women 50 . Nevertheless, the divergence in clinical outcomes after bacterial invasion of the bladder may still arise due to phenotypic differences in E. coli strains reaching the bladder that are not readily apparent in genome comparisons.…”

Urinary Microbiome: Yin and Yang of the Urinary Tract

“…Only some differences in motility genes between isolates from UTI patients and healthy individuals were found. Therefore, E. coli is part of the commensal urinary microbiota and other aspects may be determining its involvement in the development of urinary tract symptoms ( Garretto et al., 2020 ). Moreover, Escherichia coli has a greater pathogenicity in polymicrobial infections, mainly when it is isolated together with Enterococcus , although the mechanisms underlying this coinfection are not well understood ( Lavigne et al., 2008 ; Croxall et al., 2011 ).…”