Differentiation-induced uroplakin III expression promotes urothelial cell death in response to uropathogenic E. coli

Praveen Thumbikat, Ruth E. Berry, Anthony J. Schaeffer, David J. Klumpp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Uropathogenic E. coli (UPEC) expressing type 1 pili underlie most urinary tract infections (UTIs). UPEC adherence to the bladder urothelium induces a rapid apoptosis and exfoliation of terminally differentiated urothelial cells, a critical event in pathogenesis. Of the four major uroplakin proteins that are densely expressed on superficial urothelial cells, UPIa serves as the receptor for type 1-piliated UPEC, but the contributions of uroplakins to cell death are not known. We examined the role of differentiation and uroplakin expression on UPEC-induced cell death. Utilizing in vitro models of urothelial differentiation, we demonstrated induction of tissue-specific differentiation markers including uroplakins. UPEC-induced urothelial cell death was shown to increase with enhanced differentiation but required expression of uroplakin III: infection with an adenovirus encoding uroplakin III significantly increased cell death, while siRNA directed against uroplakin III abolished UPEC-induced cell death. In a murine model of UTI where superficial urothelial cells were selectively eroded to expose less differentiated cells, urothelial apoptosis was reduced, indicating a requirement for differentiation in UPEC-induced apoptosis in vivo. These data suggest that induction of uroplakin III during urothelial differentiation sensitizes cells to UPEC-induced death. Thus, uroplakin III plays a pivotal role in UTI pathogenesis.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalMicrobes and Infection
Issue number1
StatePublished - Jan 2009


  • Bladder
  • Cystitis
  • Infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases


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