Publications by Author: Toby C Chai

OBJECTIVES: To describe associations between voiding behavior and bacterial loads in a murine model of urinary tract infection (UTI).

METHODS: Fourteen female C57BL/6J mice were transurethrally inoculated with 108colony-forming unit uropathogenic E. coli (UPEC) UTI89 in 50 μL two times, 24 hours apart. Voiding spot assays were used to measure voiding behavior. Voiding spot assays and urine cultures were performed at various time points between 1 and 28 days postinfection (dpi). Bladder and kidney bacterial loads were measured at 28 dpi. Correlations were calculated between voiding spot assay variables and bacterial loads at different dpi. In a separate experiment, 3 female mice were infected with UPEC in the same manner for histology changes at 28-dpi in chronic UTI.

RESULTS: During the 28 days, among 14 mice, 8 developed chronic cystitis and 11 developed chronic pyelonephritis based on a priori definitions. All infected mice showed increased urinary frequency, polyuria, and decreased bladder capacity. Tissue fibrosis was also observed in the infected bladder. At 1 dpi and 28 dpi, the urinary bacterial loads were positively associated with frequency and polyuria. Bladder and kidney bacterial loads at 28 dpi were positively with frequency and polyuria.

CONCLUSIONS: Urine and tissue bacterial loads were associated with changes of voiding behavior at both 1 and 28 dpi.

OBJECTIVES: To analyze factors during early stage of urinary tract infection (UTI) that are associated with development of chronic UTI.

METHODS: Mice were inoculated with Uropathogenic Escherichia coli (UPEC) 2 times 24 hours apart. At 1, 3, 7, 10, 14, 21 and 28 days post infection (dpi), urine bacterial loads and voiding behavior (voiding spot assay, VSA) were measured. At 1 and 28 dpi, 32 urine inflammatory cytokines/chemokines were measured using enzyme-linked immunosorbent assay (ELISA). Bladder and kidney cytokines/chemokines were measured on 28 dpi. Mice that had no more than 1 episode of urine bacterial load < 104 colony forming unit/ml during the entire 4 weeks were defined as susceptible to chronic UTI, otherwise, mice were considered resistant.

RESULTS: At 28 dpi, 64.3% mice developed chronic UTI (susceptible group) and 35.7% mice did not (resistant group). Factors at 1 dpi that were predictive of chronic UTI included increased urine IL-2 (OR 11.9, 95%CI 1.1-130.8, P = .043) and increased urine IL-10 (OR 14.0, 95%CI 1.0-201.2, P = .052). At 28 dpi, there were several significant differences between the susceptible vs resistant groups including urine/tissue bacterial loads and certain urine/tissue cytokines/chemokines.

CONCLUSIONS: Higher urine IL-2 and IL-10 at 1 dpi predicted chronic UTI infection in this model. There have been recent publications associating both of these cytokines to UTI susceptibility. Further explorations into IL-2 and IL-10 mediated pathways could shed light on the biology of recurrent and chronic UTI which are difficult to treat.