Comparison ofEscherichia coliStrains Recovered from Human Cystitis and Pyelonephritis Infections in Transurethrally Challenged Mice

Abstract

Urinary tract infection, most frequently caused byEscherichia coli, is one of the most common bacterial infections in humans. A vast amount of literature regarding the mechanisms through which E. coli induces pyelonephritis has accumulated. Although cystitis accounts for 95% of visits to physicians for symptoms of urinary tract infections, few in vivo studies have investigated possible differences between E. coli recovered from patients with clinical symptoms of cystitis and that from patients with symptoms of pyelonephritis. Epidemiological studies indicate that cystitis-associated strains appear to differ from pyelonephritis-associated strains in elaboration of some putative virulence factors. With transurethrally challenged mice we studied possible differences using three each of the most virulent pyelonephritis and cystitis E. coli strains in our collection. The results indicate that cystitis strains colonize the bladder more rapidly than do pyelonephritis strains, while the rates of kidney colonization are similar. Cystitis strains colonize the bladder in higher numbers, induce more pronounced histologic changes in the bladder, and are more rapidly eliminated from the mouse urinary tract than pyelonephritis strains. These results provide evidence that cystitis strains differ from pyelonephritis strains in this model, that this model is useful for the study of the uropathogenicity of cystitis strains, and that it would be unwise to use pyelonephritis strains to study putative virulence factors important in the development of cystitis.

The role of cytotoxic necrotizing factor-1 in colonization and tissue injury in a murine model of urinary tract infection

“…Upon closer inspection, it was apparent that the CNF-negative mutant E. coli strain F11.297 colonized the urine, bladder and kidneys in numbers that were similar to those of the ¢rst trial. However, wild-type E. coli strain F11 colonized the urine and kidney of only one of 10 mice, a result that was discordant from the ¢rst trial and from previously published experiments [23]. In contrast, colonization of the bladder by the mutant was similar in both trials, raising doubt as to the validity of these ¢ndings.…”

“…DNA probe testing revealed that strain E. coli F11 is positive for hemolysin, P ¢mbriae, a member of the Dr family of adhesins, and aerobactin [20,22]. This strain causes cystitis in a murine model of ascending UTI and, in fact, colonizes the bladder in higher numbers than does a prototypic pyelonephritis strain [23]. The construction of E. coli strain F11.297, a CNF1-negative derivative of F11 that contains an insertion mutation in the cnf1 gene, and veri¢cation that it lacks CNF1 activity have been described previously [20].…”

“…An inoculum of approximately 2U10 9 live E. coli F11 or E. coli F11.297 was introduced into the urinary tract of female CBA/J/Hsd mice via the transurethral route. The procedures for preparation of the inoculum, transurethral challenge, documentation that re£ux of the inoculum into the kidneys did not occur and quantitative culture of kidneys, bladder and urine have been described in detail previously [23]. The geometric mean colony counts from both kidneys from each animal were analyzed as a single data point.…”

“…One half of each organ was preserved in 10% neutral bu¡ered formalin for histological examination. The procedures for tissue preparation and blinded assessment of histological changes in the kidney have been previously reported [23]. In the bladder mucosa and submucosa the degree of acute in£ammation was graded as follows.…”

Adhesion and entry of uropathogenic Escherichia coli

“…UPEC isolates, like enteric E. coli pathogens, are a genetically heterogeneous group and can vary significantly in their abilities to colonize and persist within either the bladder or the kidneys (Foxman et al, 1995;Johnson et al, 1998;Zhang et al, 2000). Epidemiological, cell culture and animal studies have indicated that a number of factors encoded by UPEC can modulate bacterial virulence within the urinary tract.…”