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Urinary Tract Infection in a Small Animal Model: Transurethral Catheterization of Male and Female Mice
Published on: December 1, 2017
Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse
Brian Becknell1, Ahmad Z Mohamed2, Birong Li3
1Nephrology Section, Nationwide Children's Hospital, Columbus, OH, United States of America; Department of Pediatrics, Ohio State University School of Medicine, Columbus, OH, United States of America; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.
Purpose:
Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI.
Methods:
Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice.
Results:
Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.
Conclusions:
CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.
Insights
Urinary stasis in Megabladder mutant mice leads to spontaneous bladder stones and increased susceptibility to urinary tract infections (UTIs) caused by opportunistic bacteria.
Area of Science:
- Urology
- Microbiology
- Genetics
Background:
- Urinary stasis is a known risk factor for recurrent urinary tract infections (UTIs).
- Homozygous mutant Megabladder (Mgb-/-) mice have congenital detrusor aplasia, leading to incomplete bladder emptying.
- This condition is hypothesized to increase susceptibility to spontaneous and experimental UTIs.
Purpose of the Study:
- To investigate the predisposition of Mgb-/- mice to spontaneous and experimental UTIs.
- To determine the role of urinary stasis in the pathogenesis of UTIs in Mgb-/- mice.
Main Methods:
- Mice (Mgb-/-, Mgb+/-, and wild-type) underwent serial ultrasound and urine cultures.
- Bacterial isolates were identified, and bladder stones were analyzed.
- Histologic analysis of bladders and kidneys was performed.
- Pathogenicity of coagulase-negative Staphylococcus (CONS) was tested, and the effect of urinary stasis was evaluated via vesicostomy.
Main Results:
- Mgb-/- mice developed spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks.
- CONS was the sole isolate from bladder stones in Mgb-/- mice.
- Histologic analysis revealed mucosal injury, inflammation, and fibrosis in bladders and kidneys with stones.
- Transurethral CONS inoculation caused cystitis and pyelonephritis in Mgb-/- mice, but not wild-type controls.
- Vesicostomy reduced bacterial load in Mgb-/- mice after CONS inoculation.
Conclusions:
- Coagulase-negative Staphylococcus (CONS) acts as an opportunistic uropathogen in the context of urinary stasis.
- Urinary stasis in Mgb-/- mice significantly enhances UTI incidence and severity.
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