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Updated: Jun 24, 2026

An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection
Published on: June 24, 2025
Tamm-horsfall protein protects against urinary tract infection by proteus mirabilis
Hajamohideen S Raffi1, James M Bates, Zoltan Laszik
1Department of Medicine/Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Purpose:
Proteus mirabilis is a common cause of urinary tract infection. We determined the role of Tamm-Horsfall protein as a host defense factor against the cystitis and pyelonephritis caused by P. mirabilis.
Materials And Methods:
We generated Tamm-Horsfall protein gene knockout mice using homologous recombination. We introduced P. mirabilis transurethrally into the bladder of Tamm-Horsfall protein deficient (THP(-/-)) and genetically similar WT (THP(+/+)) mice. We cultured urine to quantitate the degree of bacteriuria. We examined bladders and kidneys grossly and histomorphometrically to determine the intensity of inflammation.
Results:
THP(-/-) mice had more severe bacteriuria and cystitis than THP(+/+) mice. THP(-/-) mice had more pyelonephritic abscesses than THP(+/+) mice. The severity of histological pyelonephritis on semiquantitative histomorphometric analysis appeared to be greater in THP(-/-) mice. The difference between the 2 groups approached but did not attain statistical significance (p = 0.053).
Conclusion:
Tamm-Horsfall protein acts as a host defense factor against P. mirabilis induced urinary tract infection.
Insights
Tamm-Horsfall protein (THP) protects against Proteus mirabilis urinary tract infections. Mice lacking THP showed increased bacteria, cystitis, and pyelonephritis, indicating THP
Area of Science:
- Urology
- Microbiology
- Immunology
Background:
- Proteus mirabilis frequently causes urinary tract infections (UTIs).
- Tamm-Horsfall protein (THP) is a key urinary glycoprotein with potential host defense functions.
Purpose of the Study:
- To investigate the role of THP as a host defense mechanism against P. mirabilis-induced cystitis and pyelonephritis.
- To elucidate the impact of THP deficiency on the severity of P. mirabilis UTI.
Main Methods:
- Generation of THP gene knockout (THP(-/-)) and wild-type (THP(+/+)) mice.
- Transurethral inoculation of P. mirabilis into mouse bladders.
- Quantification of bacteriuria and histomorphometric analysis of bladder and kidney inflammation.
Main Results:
- THP(-/-) mice exhibited significantly higher bacteriuria and cystitis severity compared to THP(+/+) mice.
- A greater incidence of pyelonephritic abscesses was observed in THP(-/-) mice.
- Histological analysis suggested increased pyelonephritis severity in THP(-/-) mice, though not statistically significant (p=0.053).
Conclusions:
- Tamm-Horsfall protein functions as a crucial host defense factor against P. mirabilis-induced UTIs.
- THP deficiency exacerbates bacterial load and inflammatory responses in the urinary tract.
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