Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli

Lan Mo, Xin Hua Zhu, Hong Ying Huang, Ellen Shapiro, David L. Hasty, Xue Ru Wu

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The adhesion of uropathogenic Escherichia coli to the urothelial surface of the bladder is a prerequisite for the establishment of bladder infections. This adhesion process relies on E. coli adhesins and their cognate urothelial receptors, and it also is influenced by an intricate array of defense mechanisms of the urinary system. In this study, we examined the in vivo role of Tamm-Horsfall protein (THP), the most abundant urinary protein, in innate urinary defense. We genetically ablated the mouse THP gene and found that THP deficiency predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation of too few type 1-fimbriated E. coli to colonize wild-type mice caused significant bladder colonization in THP-knockout mice. In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder. Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble "receptor," binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface. These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections. The generation of THP-deficient mice established the role of THP as a first line of urinary defense and should help elucidate other potential functions of this major protein in urinary tract physiology and diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number4 55-4
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Uromodulin
Urinary Bladder
Escherichia coli
Genes
Protein Deficiency
Uroplakin Ia
Urinary Tract Physiological Phenomena
Escherichia coli Adhesins
Uropathogenic Escherichia coli
Urologic Diseases
Infection
Bacterial Infections
Knockout Mice
Proteins

Keywords

  • FimH adhesin
  • Gene knockout
  • Innate host defense
  • Urinary bladder infection

ASJC Scopus subject areas

  • Physiology

Cite this

Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli. / Mo, Lan; Zhu, Xin Hua; Huang, Hong Ying; Shapiro, Ellen; Hasty, David L.; Wu, Xue Ru.

In: American Journal of Physiology - Renal Physiology, Vol. 286, No. 4 55-4, 04.2004.

Research output: Contribution to journalArticle

Mo, Lan ; Zhu, Xin Hua ; Huang, Hong Ying ; Shapiro, Ellen ; Hasty, David L. ; Wu, Xue Ru. / Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli. In: American Journal of Physiology - Renal Physiology. 2004 ; Vol. 286, No. 4 55-4.
@article{2ddce9e56f6e4cefb182b89b80424c43,
title = "Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli",
abstract = "The adhesion of uropathogenic Escherichia coli to the urothelial surface of the bladder is a prerequisite for the establishment of bladder infections. This adhesion process relies on E. coli adhesins and their cognate urothelial receptors, and it also is influenced by an intricate array of defense mechanisms of the urinary system. In this study, we examined the in vivo role of Tamm-Horsfall protein (THP), the most abundant urinary protein, in innate urinary defense. We genetically ablated the mouse THP gene and found that THP deficiency predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation of too few type 1-fimbriated E. coli to colonize wild-type mice caused significant bladder colonization in THP-knockout mice. In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder. Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble {"}receptor,{"} binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface. These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections. The generation of THP-deficient mice established the role of THP as a first line of urinary defense and should help elucidate other potential functions of this major protein in urinary tract physiology and diseases.",
keywords = "FimH adhesin, Gene knockout, Innate host defense, Urinary bladder infection",
author = "Lan Mo and Zhu, {Xin Hua} and Huang, {Hong Ying} and Ellen Shapiro and Hasty, {David L.} and Wu, {Xue Ru}",
year = "2004",
month = "4",
language = "English (US)",
volume = "286",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4 55-4",

}

TY - JOUR

T1 - Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli

AU - Mo, Lan

AU - Zhu, Xin Hua

AU - Huang, Hong Ying

AU - Shapiro, Ellen

AU - Hasty, David L.

AU - Wu, Xue Ru

PY - 2004/4

Y1 - 2004/4

N2 - The adhesion of uropathogenic Escherichia coli to the urothelial surface of the bladder is a prerequisite for the establishment of bladder infections. This adhesion process relies on E. coli adhesins and their cognate urothelial receptors, and it also is influenced by an intricate array of defense mechanisms of the urinary system. In this study, we examined the in vivo role of Tamm-Horsfall protein (THP), the most abundant urinary protein, in innate urinary defense. We genetically ablated the mouse THP gene and found that THP deficiency predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation of too few type 1-fimbriated E. coli to colonize wild-type mice caused significant bladder colonization in THP-knockout mice. In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder. Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble "receptor," binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface. These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections. The generation of THP-deficient mice established the role of THP as a first line of urinary defense and should help elucidate other potential functions of this major protein in urinary tract physiology and diseases.

AB - The adhesion of uropathogenic Escherichia coli to the urothelial surface of the bladder is a prerequisite for the establishment of bladder infections. This adhesion process relies on E. coli adhesins and their cognate urothelial receptors, and it also is influenced by an intricate array of defense mechanisms of the urinary system. In this study, we examined the in vivo role of Tamm-Horsfall protein (THP), the most abundant urinary protein, in innate urinary defense. We genetically ablated the mouse THP gene and found that THP deficiency predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation of too few type 1-fimbriated E. coli to colonize wild-type mice caused significant bladder colonization in THP-knockout mice. In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder. Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble "receptor," binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface. These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections. The generation of THP-deficient mice established the role of THP as a first line of urinary defense and should help elucidate other potential functions of this major protein in urinary tract physiology and diseases.

KW - FimH adhesin

KW - Gene knockout

KW - Innate host defense

KW - Urinary bladder infection

UR - http://www.scopus.com/inward/record.url?scp=1642306406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642306406&partnerID=8YFLogxK

M3 - Article

C2 - 14665435

AN - SCOPUS:1642306406

VL - 286

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4 55-4

ER -