Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriatedEscherichia coli
- 1 April 2004
- journal article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 286 (4), F795-F802
- https://doi.org/10.1152/ajprenal.00357.2003
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
This publication has 59 references indexed in Scilit:
- Assessment of Virulence of Uropathogenic Escherichia coli Type 1 Fimbrial Mutants in Which the Invertible Element Is Phase-Locked On or OffInfection and Immunity, 2002
- Prevalence and Predictors of Trimethoprim‐Sulfamethoxazole Resistance among UropathogenicEscherichia coliIsolates in MichiganClinical Infectious Diseases, 2002
- Analysis of the C-Terminal Structure of Urinary Tamm–Horsfall Protein Reveals That the Release of the Glycosyl Phosphatidylinositol-Anchored Counterpart from the Kidney Occurs by Phenylalanine-Specific ProteolysisBiochemical and Biophysical Research Communications, 2001
- Mechanism of Release of Urinary Tamm-Horsfall Glycoprotein from the Kidney GPI-Anchored CounterpartBiochemical and Biophysical Research Communications, 2001
- Evaluation of Urinary Tamm–Horsfall Protein in Post-Menopausal Diabetic WomenJournal of Diabetes and its Complications, 1999
- Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract.Proceedings of the National Academy of Sciences of the United States of America, 1996
- GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney.Proceedings of the National Academy of Sciences of the United States of America, 1992
- Type 1 fimbriae mutants of Escherichia coli K12: characterization of recognized afimbriate strains and construction of new fim deletion mutantsMolecular Microbiology, 1991
- Structural analysis of the preponderant high-mannose oligosaccharide of human Tamm-Horsfall glycoproteinCarbohydrate Research, 1988
- Abnormal radiofurosemide binding by Tamm Horsfall glycoprotein of diabetic patientsDiabetologia, 1985