Genomic Diversity and Fitness of E. coli Strains Recovered from the Intestinal and Urinary Tracts of Women with Recurrent Urinary Tract Infection

Abstract

Urinary tract infections (UTIs) are common in women and recurrence is a major clinical problem. Most UTIs are caused by uropathogenic Escherichia coli (UPEC). UPEC are generally thought to migrate from the gut to the bladder to cause UTI. UPEC strains form specialized intracellular bacterial communities (IBCs) in the bladder urothelium as part of a pathogenic mechanism to establish a foothold during acute stages of infection. Evolutionarily, such a specific adaptation to the bladder environment would be predicted to result in decreased fitness in other habitats, such as the gut. To examine this concept, we characterized 45 E. coli strains isolated from the feces and urine of four otherwise healthy women with recurrent UTIs. Multi-locus sequence typing revealed that two of the patients maintained a clonal population in both of these body habitats throughout their recurrent UTIs, whereas the other two manifested a wholesale shift in the dominant UPEC strain colonizing their urinary tract and gut between UTIs. These results were confirmed when we subjected 26 isolates from two patients, one representing the persistent clonal pattern and the other representing the dynamic population shift, to whole genome sequencing. In vivo competition studies conducted in mouse models of bladder and gut colonization, using isolates taken from one of the patients with a wholesale population shift, and a newly developed SNP-based method for quantifying strains, revealed that the strain that dominated in her last UTI episode had increased fitness in both body habitats relative to the one that dominated in the preceding episodes. Furthermore, increased fitness was correlated with differences in the strains’ gene repertoires and their in vitro carbohydrate and amino acid utilization profiles. Thus, UPEC appear capable of persisting in both the gut and urinary tract without a fitness tradeoff. Determination of all of the potential reservoirs for UPEC strains that cause recurrent UTI will require additional longitudinal studies of the type described in this report, with sampling of multiple body habitats during and between episodes.

The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli

“…However, surface association via type 1 pili favors the phase fim ON state, even in the presence of urine. In the context of human colonization/infection, UPEC-host interactions take place in several oxygen gradients; in the gastrointestinal tract, where UPEC can reside as a reservoir (48), the oxygen tension can vary between 3 and 60 torr (0.4% to 8.4%) depending on the location (49). Upon exit into the environment, the oxygen tension surges to 21% and then drops again significantly (to 4% to 7%) in the bladder lumen (50).…”

A retrospective study of antibiotic sensitivity pattern of uropathogens in the Federal Capital Territory, Nigeria

“…UTIs also known as cystitis (bladder infection) when it affects the lower urinary tract and pyelonephritis (kidney infection) when it affects the upper urinary tract. In the lower urinary tract, it is characterized by burning sensation with either frequent urination or urge to urinate or both with significant pain (Nicole, 2008), although these symptoms may vary from mild to severe (Lane and Takhar, 2011;Chen et al, 2013). In healthy women, the pain lasts an average of six days (Colgan and Williams, 2011).…”

“…In healthy women, the pain lasts an average of six days (Colgan and Williams, 2011). However, in the upper urinary tract, it is characterized by flank pain, fever or nausea (Lane and Takhar, 2011;Chen et al, 2013). The most predominant etiologic agent of UTI is the Escherichia coli causing about 80 to 85% of the cases of UTIs, with Staphylococcus being the cause in 5 to 10% (Chen et al, 2013;Nicole, 2008).…”

“…However, in the upper urinary tract, it is characterized by flank pain, fever or nausea (Lane and Takhar, 2011;Chen et al, 2013). The most predominant etiologic agent of UTI is the Escherichia coli causing about 80 to 85% of the cases of UTIs, with Staphylococcus being the cause in 5 to 10% (Chen et al, 2013;Nicole, 2008). The prevalence of UTIs in women may be due to the proximity of the urethra to the anus (Aboderi et al, 2009;DeBacker et al, 2008).…”

Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

“…In contrast, UPEC strains appear to rarely cause problems within the gut but can elicit disease when given access to alternative niches such as the urinary tract or bloodstream. UPEC strains originating from the gut are likely the primary cause of UTIs (25), but the factors that promote UPEC fitness within the intestinal tract are just beginning to come to light (26)(27)(28).…”