BACKGROUND: Human colon contains many bacteria that commonly colonize the perineum and frequently enter the urinary tract. Uropathogenic Escherichia coli are the most common cause of urinary tract infection. Type 1 fimbriated E. coli have been associated with cystitis, and P fimbriated E. coli with pyelonephritis. Factors involved in clearing bacteria from the urinary tract are poorly understood. Tamm-Horsfall protein (THP), the most abundant protein in mammalian urine, has been postulated to play a role in defense against urinary tract infection but definitive proof for this idea has been lacking. METHODS: In this study, we generated THP gene knockout mice by the technique of homologous recombination, and examined if the THP-deficient (THP-/-) mice were more prone to urinary tract infection. Various strains of E. coli expressing type 1 or P fimbriae were introduced transurethrally into the bladders of the THP-/- and genetically similar wild-type (THP+/+) mice. Urine, bladder, and kidney tissues were obtained from the mice and cultured for bacterial growth. RESULTS: THP-/- mice inoculated with type 1 fimbriated E. coli had a longer duration of bacteriuria, and more intense colonization of the urinary bladder in comparison with THP+/+ mice. When inoculated with a P fimbriated strain of E. coli, the THP-/- mice showed no difference in kidney bacterial load when compared with the THP+/+ mice. CONCLUSION: These findings support the idea that THP serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract.
BACKGROUND:Human colon contains many bacteria that commonly colonize the perineum and frequently enter the urinary tract. Uropathogenic Escherichia coli are the most common cause of urinary tract infection. Type 1 fimbriated E. coli have been associated with cystitis, and P fimbriated E. coli with pyelonephritis. Factors involved in clearing bacteria from the urinary tract are poorly understood. Tamm-Horsfall protein (THP), the most abundant protein in mammalian urine, has been postulated to play a role in defense against urinary tract infection but definitive proof for this idea has been lacking. METHODS: In this study, we generated THP gene knockout mice by the technique of homologous recombination, and examined if the THP-deficient (THP-/-) mice were more prone to urinary tract infection. Various strains of E. coli expressing type 1 or P fimbriae were introduced transurethrally into the bladders of the THP-/- and genetically similar wild-type (THP+/+) mice. Urine, bladder, and kidney tissues were obtained from the mice and cultured for bacterial growth. RESULTS:THP-/- mice inoculated with type 1 fimbriated E. coli had a longer duration of bacteriuria, and more intense colonization of the urinary bladder in comparison with THP+/+ mice. When inoculated with a P fimbriated strain of E. coli, the THP-/- mice showed no difference in kidney bacterial load when compared with the THP+/+ mice. CONCLUSION: These findings support the idea that THP serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract.
Authors: Thomas J Hannan; Makrina Totsika; Kylie J Mansfield; Kate H Moore; Mark A Schembri; Scott J Hultgren Journal: FEMS Microbiol Rev Date: 2012-05 Impact factor: 16.408
Authors: Tarek M El-Achkar; Ruth McCracken; Yan Liu; Monique R Heitmeier; Soline Bourgeois; Jan Ryerse; Xue-Ru Wu Journal: Am J Physiol Renal Physiol Date: 2013-02-06
Authors: Matt S Conover; Ségolène Ruer; Joemar Taganna; Vasilios Kalas; Henri De Greve; Jerome S Pinkner; Karen W Dodson; Han Remaut; Scott J Hultgren Journal: Cell Host Microbe Date: 2016-09-22 Impact factor: 21.023