Bacteria-induced uroplakin signaling mediates bladder response to infection (PloS Pathog, 2009, 5(5):e1000415)

報告日期: 2010/05/04
報告時間: 17:10/18:00
報告學生: 黃文俊
講評老師: 曾進忠

Bacteria-induced uroplakin signaling mediates bladder response to infection

Praveen Thumbikat et al.

PLoS Pathogens, 2009, 5: e1000415


Presenter: 黃文俊

Commentator:曾進忠 醫師

Date: 2010/5/4, 17:10-18:00

Place: Room 602, College of medicine



    Uropathogenic Escherichia coli (UPEC) are responsible for about 80% of the urinary tract infections (UTIs).To colonize bladder urothelial cell is the first and essential step to UPEC for further infection. Uroplakins on bladder urothelial cell surface, including UP Ia, Ib, II, IIIa, are involved in bladder permeability barrier.

UP Ia also play an important role in UPEC colonization by serving as the receptor for UPEC’s type 1 pili adhesin FimH. Binding of type 1 pili to mannosylated uroplakins promotes bacterial invasion of urothelial cell and induces urothelial cell apoptosis. Invasion into bladder urothelial cells contributes to UPEC evasion from immune system killing and this effect is considered to be a main cause of recurrent UTI.

Urothelial cell apoptosis is a host defense mechanism that contributes to bacterial clearance by ridding bladder urothelial cell-associated bacteria during voiding. Up to now, the signal transduction involved in bacterial invasion and apoptosis of urothelial cells have not been clearly identified. Upon infection with UPEC, urothelial cells also secrete inflammatory chemokines, such as IL-8 which recruits neutrophils to the infection site for bacterial clearance.

    In this study, the authors firstly found that FimH interacted with four uroplakins and induced phosphorylation of threonine-244 on the UPIIIa cytoplasmic tail by casein kinase II (CK2). These results indicated that UPIIIa might function as a signal transducer. The phosphorylation of threonine-244 on the UPIIIa initiated the elevation of intracellular calcium derived from both intracellular and extracellular pool. In addition, inhibition of CK2 activity and knockdown of CK2 expression decreased bacterial invasion. They also found that both inhibition of CK2 activity and knockdown of UPIIIa expression decreased urothelial apoptosis induced by FimH.

Finally, knockdown of UPIIIa didn’t affect UPEC induced-urothelial inflammatory responses, such as IL-8 secretion and neutrophil influx. Taken together, these data suggested that UPIIIa signaling play an important role in bacterial invasion and FimH-induced urothelial apoptosis but not in inflammation responses. Their studies suggested that Casein kinase II and calcium might be novel therapeutic targets for intervention UTI by inhibiting the UPEC invasion.



1.    Wu, X. R., X. P. Kong, et al. Uroplakins in urothelial biology, function, and disease. Kidney Int, v.75, n.11, Jun, p.1153-65. 2009.