Tamm-Horsfall Protein Protects Against Urinary Tract Infection by Proteus Mirabilis

Department of Medicine/Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
The Journal of urology (Impact Factor: 4.47). 04/2009; 181(5):2332-8. DOI: 10.1016/j.juro.2009.01.014
Source: PubMed


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.
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.
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).
Tamm-Horsfall protein acts as a host defense factor against P. mirabilis induced urinary tract infection.

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    • "The role of THP as a urinary defense factor was highlighted when we and others created THP gene knockout mice and demonstrated that THP-deficient mice had difficulty clearing E. coli from the urinary tract [10,11]. Subsequently, we extended these findings to include other uropathogenic bacteria such as Klebsiella pneumonia, Staphylococcus saprophyticus, [19] and Proteus mirabilis[20]. In a study examining 51 long term catheterized patients, the bacterial isolates from UTI episodes longer than 2 weeks expressed type 1 fimbriae more frequently and bound more THP than bacterial isolates from UTI episodes lasting 1 week or less [21]. "
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    ABSTRACT: Background Urinary catheters are associated, commonly with bacteriuria and frequently with urinary tract infection. Tamm-Horsfall Protein (THP) is urine's most abundant protein and is known to bind to uropathogenic bacteria. The role of THP in the pathogenesis of catheter associated urinary tract infection (CAUTI) is not clear. We examined the role of THP in facilitating bacterial binding to urinary catheters in vivo and in vitro. Findings Twenty one urinary catheters were obtained from 20 hospitalized patients. THP was eluted from the catheter surface and catheter segments were cultured. Additional studies were performed in vitro on unused silicone and latex catheters to determine the binding of THP, and the effect of THP on the binding of Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), to the catheter surface. On catheters obtained from patients, the THP deposition was significantly more on culture positive catheters than on culture negative catheters. In the in vitro studies, THP bound to both silicone and latex catheters, and THP enhanced the adherence of E. coli and P. aeruginosa to both types of catheters. Conclusion THP binds to urinary catheters and facilitates the binding of uropathogenic bacteria to catheters.
    BMC Research Notes 09/2012; 5(1):532. DOI:10.1186/1756-0500-5-532
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    • "THP had been linked to water/electrolyte balance and to kidney innate immunity [19]. THP may act as a host defense factor against Proteus mirabilis induced urinary tract infection [20], and also, as an inhibitor of urinary stone formation and adhesion [21]. Mutations in the gene encoding uromodulin lead to uromodulinassociated kidney diseases, characterized by progressive tubulointerstitial damage, impaired urinary concentrating ability, hyperuricemia, renal cysts and progressive renal failure. "
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    ABSTRACT: Mutations in the UMOD gene encoding uromodulin (Tamm-Horsfall glycoprotein) result in the autosomal dominant transmission of progressive renal insufficiency and hypo-uricosuric hyperuricemia leading to gout at an early age. The clinical appearance is characterized by renal insufficiency and gout occurring in the late teenage years, with end-stage kidney disease characteristically developing between 40 and 70 years of age. This report provides a long-term characterization of renal functional decline in three children from one family with a novel UMOD mutation (c.891T>G, p.C297W) who received allopurinol and a low protein diet. While renal functional decline is slow in individuals with UMOD mutations, it may appear early in life and be associated with marked hyperuricemia. Anemia was also noted in this family.
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