Bacteria-induced uroplakin signaling mediates bladder response to infection.
Urinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apo...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000415&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850240605197697024 |
|---|---|
| author | Praveen Thumbikat Ruth E Berry Ge Zhou Benjamin K Billips Ryan E Yaggie Tetiana Zaichuk Tung-Tien Sun Anthony J Schaeffer David J Klumpp |
| author_facet | Praveen Thumbikat Ruth E Berry Ge Zhou Benjamin K Billips Ryan E Yaggie Tetiana Zaichuk Tung-Tien Sun Anthony J Schaeffer David J Klumpp |
| author_sort | Praveen Thumbikat |
| collection | DOAJ |
| description | Urinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apoptosis of urothelial cells. FimH initiates bladder pathology by binding to the uroplakin receptor complex, but the subsequent events mediating pathogenesis have not been fully characterized. We report a hitherto undiscovered signaling role for the UPIIIa protein, the only major uroplakin with a potential cytoplasmic signaling domain, in bacterial invasion and apoptosis. In response to FimH adhesin binding, the UPIIIa cytoplasmic tail undergoes phosphorylation on a specific threonine residue by casein kinase II, followed by an elevation of intracellular calcium. Pharmacological inhibition of these signaling events abrogates bacterial invasion and urothelial apoptosis in vitro and in vivo. Our studies suggest that bacteria-induced UPIIIa signaling is a critical mediator of bladder responses to insult by uropathogenic E. coli. |
| format | Article |
| id | doaj-art-be99d1795d0047bfb61aa5736bbf47ca |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2009-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-be99d1795d0047bfb61aa5736bbf47ca2025-08-20T02:00:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-05-0155e100041510.1371/journal.ppat.1000415Bacteria-induced uroplakin signaling mediates bladder response to infection.Praveen ThumbikatRuth E BerryGe ZhouBenjamin K BillipsRyan E YaggieTetiana ZaichukTung-Tien SunAnthony J SchaefferDavid J KlumppUrinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apoptosis of urothelial cells. FimH initiates bladder pathology by binding to the uroplakin receptor complex, but the subsequent events mediating pathogenesis have not been fully characterized. We report a hitherto undiscovered signaling role for the UPIIIa protein, the only major uroplakin with a potential cytoplasmic signaling domain, in bacterial invasion and apoptosis. In response to FimH adhesin binding, the UPIIIa cytoplasmic tail undergoes phosphorylation on a specific threonine residue by casein kinase II, followed by an elevation of intracellular calcium. Pharmacological inhibition of these signaling events abrogates bacterial invasion and urothelial apoptosis in vitro and in vivo. Our studies suggest that bacteria-induced UPIIIa signaling is a critical mediator of bladder responses to insult by uropathogenic E. coli.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000415&type=printable |
| spellingShingle | Praveen Thumbikat Ruth E Berry Ge Zhou Benjamin K Billips Ryan E Yaggie Tetiana Zaichuk Tung-Tien Sun Anthony J Schaeffer David J Klumpp Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathogens |
| title | Bacteria-induced uroplakin signaling mediates bladder response to infection. |
| title_full | Bacteria-induced uroplakin signaling mediates bladder response to infection. |
| title_fullStr | Bacteria-induced uroplakin signaling mediates bladder response to infection. |
| title_full_unstemmed | Bacteria-induced uroplakin signaling mediates bladder response to infection. |
| title_short | Bacteria-induced uroplakin signaling mediates bladder response to infection. |
| title_sort | bacteria induced uroplakin signaling mediates bladder response to infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000415&type=printable |
| work_keys_str_mv | AT praveenthumbikat bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT rutheberry bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT gezhou bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT benjaminkbillips bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT ryaneyaggie bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT tetianazaichuk bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT tungtiensun bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT anthonyjschaeffer bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection AT davidjklumpp bacteriainduceduroplakinsignalingmediatesbladderresponsetoinfection |