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Abstract: SA-PO433

Dual Role for the Uroplakin Plaque in Establishment and Maintenance Phases of Urinary Tract Infection

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Li, Birong, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Jackson, Ashley R., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Becknell, Brian, Nationwide Children's Hospital, Columbus, Ohio, United States
Background

Uropathogenic Escherichia coli (UPEC) account for up to 90% of human urinary tract infections (UTI). Specialized epithelial cells of the bladder produce glycosylated uroplakin (Upk) plaques, which bind to type I fimbriae of UPEC in a mannose-dependent manner. Here we evaluated the role and regulation of the Upk plaque during experimental UTI.

Methods

We established acute experimental UTI in 6-8 week old female Upk1b-/- and FVB/N mice by transurethral inoculation of UPEC or Enterococcus faecalis. Intracellular bacterial communities were detected based on β-galactosidase activity. Upk proteins were localized by immunohistochemistry, and plaque ultrastructure was visualized by transmission electron microscopy. Urothelial barrier function was evaluated on the basis of permeability to FITC-Dextran. We modeled chronic UTI by UPEC inoculation of 6-8 week old female C3H/HeOuJ mice.

Results

Upk1b deletion results in absent uroplakin plaque on the apical surface of bladder epithelial cells and increased permeability to FITC-Dextran. While intracellular bacterial communities were easily detectable in control urothelium, Upk1b-/- bladders lacked these intracellular reservoirs of UPEC entirely. Moreover, Upk1b loss led to reduced neutrophil infiltration of the bladder urothelium. Consistent with the failure of UPEC to invade the epithelium in the absence of the Upk plaque, Upk1b-/- mice exhibited reduced UPEC urinary tract colonization compared to controls (p < 0.05, Mann-Whitney U test). In contrast, Upk plaque loss did not impact the ability of Enterococcus faecalis to establish experimental UTI. When UTI were established in the chronic C3H/HeOuJ model, Upk mRNA and Upk protein levels decreased rapidly and remained suppressed for up to 4 weeks following infection.

Conclusion

Upk1b is critically required for Upk plaque assembly in superficial bladder epithelial cells. The Upk plaque initially facilitates UPEC invasion of the bladder, but this structure is dispensable for maintenance of infection, as chronic UTI results in downregulation of Upk plaque assembly at the mRNA and protein levels.

Funding

  • NIDDK Support