Escherichia Coli ST131 Collected From Companion Animals Can Cause Cystitis and Pyelonephritis in a Murine Model of Urinary Tract Infection
Background: Uropathogenic Escherichia coli (UPEC) cause 80% of uncomplicated urinary tract infections (UTI) globally. Since the mid- 2000s, a subset of UPEC called ST131 have undergone rapid pandemic spread. ST131 are a major cause of UTIs that lead to serious complications in humans like pyelonephritis and sepsis. In companion animals, ST131 infections rarely cause severe symptoms, but are underreported as tracking of infections in animals has been limited. Recent analyses have shown that ST131 infections in companion animals represent spread from human hosts not primary animal infections. To manage the risk of zoonotic spread of ST131 E. coli from companion animals to humans, it is vital to understand the bidirectional transmission and identify the factors that predict an isolate’s ability to cause severe disease. The purpose of this study was to determine whether ST131 isolates from companion animals retain the ability, like their human counterparts, to cause UTI and pyelonephritis in a mouse model of UTI and to evaluate mechanisms of motility and adhesion. Methods: Six ST131 isolates collected from 3 dogs and 3 cats, were transurethrally inoculated into 36 C57BL/6 mice. CFUs were determined from urine, and bladder and kidney tissue post sacrifice. Isolates were assessed for motility via RNA expression of two flagellar genes, soft agar and trans-well assays. Adhesion was assessed via mannose sensitive hemagglutination, and T24 bladder epithelia adhesion assay. Finally, the percentage of a population of each isolate with type 1 fimbriae turned on was determined. Results: E. coli ST131 (102 – 1011 CFUs) were present in the urine ≥ 21 days in 24 of 36 mice. All 6 strains of E. coli were able to infect the kidney with strain AUS75 infecting 1/6 mice while strain AUS272 infected 4/6 mice. Three strains infected 2/6 mice and one strain (AUS80) 3/6 mice. The diameters of the motility assays ranged from 4.3 (AUS80) to 38mm (AUS75). flhD RNA expression ranged from 3- (AUS75) to 13-fold (AUS272) and flgE expression from 7- to 414 (AUS80) -fold compared to the control strain. All but one isolate (AUS80) moved through the trans-well toward LB broth while only three (AUS101, AUS125, and HV266) moved in response to urine. Only two isolates (AUS101 and AUS272) were able to agglutinate red blood cells after more than a 2-fold dilution. T24 adhesion ranged from 0.14% (AUS75) to 21.1% (AUS101) in static culture and from 0.85% (AUS75) to 7.0% (AUS101) in shaking culture. The only isolate that was more adherent under static conditions than shaking was AUS101. The average percentage of a population with fimS turned ON under static culture conditions ranged from 9.67% (HV266) to 83.67% (AUS272). Conclusions: Previous data from our lab showed that human ST131 isolates were able to reach the kidney at higher rates than non-ST131 isolates. The animal isolates in this study were able to reach the kidney at rates comparable to the human associated ST131 isolates. This indicates the risk of severe infection is maintained if transmitted back to a human host. Isolates with enhanced motility or those that were attracted to urine or LB did not correlate with the isolates that were more successful at ascending the ureters to the kidneys suggesting that only basal levels of motility are required for ascension of the ureters. Isolates that were more adhesive or had a higher percentage of fimS turned on did not correlate with colonization of the bladder or ascension to the kidneys suggesting that adhesion mediated by type 1 fimbriae may play a smaller role in UTIs than previously thought.
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