Escherichia coli is the predominant pathogen in urinary tract infections. Fimbriae are one of the major virulence factors of these bacteria, since these protein appendices contribute towards bacterial adhesion to epithelial cells. In clinical E. coli isolates from urinary tract infections, P fimbriae are more frequently present than S fimbriae. However, these two types of fimbriae mediate adhesion to cultured tubular epithelial cells equally well. Tamm-Horsfall protein, which is the most abundant protein in normal human urine, inhibits hemagglutination by E. coli expressing S fimbriae, but does not interfere with hemagglutination by P-fimbriated E. coli. Therefore, it has been speculated that Tamm-Horsfall protein may serve as a clearance factor for S-fimbriated E. coli in human urine. In our experiments, adherence of purified S fimbriae and of S-fimbriated E. coli to tubular epithelial cells was inhibited by Tamm-Horsfall protein, but the protein also decreased binding of P-fimbriated E. coli to approximately the same degree. We found less adherence of both types of fimbriae to a Madin-Darby canine kidney cell line expressing soluble and membrane-bound Tamm-Horsfall protein as compared with the control cell line. In conclusion, our in vitro data suggest that urinary Tamm-Horsfall protein may serve as a clearance factor for E. coli expressing both S and P fimbriae. In the light of these findings, the low clinical relevance of S-fimbriated E. coli for urinary tract infections may be readily explained; however, the predominance of P fimbriae remains unresolved.

Many factors increase pathogenicity of uropathogenic Escherichia coli. Among them, fimbriae play a major role, since these protein appendices contribute towards bacterial adhesion to uroepithelial cells. In clinical Escherichia coli isolates from urinary tract infections, P fimbriae are more frequently present than S fimbriae, though both types of fimbriae mediate adhesion to cultured tubular epithelial cells equally well. The incongruity between clinical relevance and adherence capacity led to the hypothesis that there is an urinary factor which inhibits S fimbrial but not P fimbrial adherence. Tamm-Horsfall protein, which is produced in cells from the loop of Henle and the distal tubule, inhibits hemagglutination by S, but nor P fimbriated Escherichia coli. We examined the effect of Tamm-Horsfall protein on fimbrial adherence of Escherichia coli to tubular epithelial cells and found adherence of S and P fimbriated Escherichia coli significantly reduced. The effect was specific and dose-dependent. In conclusion, these data may explain the low clinical relevance of S fimbriaeted Escherichia coli, but not the predominance of P fimbriated.