title: Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.
abstract: OBJECTIVE
  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.
authors.affiliation: Nephrology 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.affiliation: Department of Urology, University of Louisville, Louisville, KY, United States of America.
authors.forename: Ahmad Z
authors.initials: AZ
authors.lastname: Mohamed
authors.affiliation: Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.
authors.forename: Birong
authors.initials: B
authors.lastname: Li
authors.affiliation: Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wilhide
authors.affiliation: Nephrology 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.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ingraham
mesh_terms: D000818:Animals; D001437:Bacteriuria / Q000150:complications / Q000382:microbiology; D003556:Cystitis / Q000150:complications; D004198:Disease Susceptibility; D005260:Female; D006863:Hydrogen-Ion Concentration; D017616:Magnesium Compounds; D051379:Mice; D008817:Mice, Mutant Strains; D010710:Phosphates; D011704:Pyelonephritis / Q000150:complications; D013210:Staphylococcus / Q000502:physiology*; D000069877:Struvite; D001743:Urinary Bladder / Q000473:pathology; D014547:Urinary Diversion; D014551:Urinary Tract / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000209:etiology* / Q000382:microbiology*; D052878:Urolithiasis / Q000150:complications*
chemical_list: D017616:Magnesium Compounds; D010710:Phosphates; D000069877:Struvite