Identification of factors in human urine that inhibit the binding of Escherichia coli adhesins.
Earlier studies on the binding of Escherichia coli adhesins to the human urinary tract have indicated that the ability to recognize binding sites on the urinary tract epithelial cells is not a characteristic for P fimbriae only, but is also shared by some other adhesins that are not associated with pyelonephritis, especially S fimbriae. In the present study we have investigated whether human urine contains inhibitors of the binding of E. coli adhesins. Normal human urine was found to inhibit hemagglutination by S and type 1 fimbriae but not P fimbriae. The major inhibitor of S fimbriae in normal urine was identified as Tamm-Horsfall glycoprotein, and the interaction with S fimbriae is probably mediated by its sialyloligosaccharide chains. No significant variation was observed in the inhibitory effect of T-H glycoprotein preparations originating from different individuals. In contrast to S fimbriae, the major inhibitors of type 1 fimbriae in urine were identified as low-molecular-weight compounds. Gel filtration and ion-exchange chromatography and alpha-mannosidase treatment indicated that they were neutral alpha-mannosides, probably manno-oligosaccharides with three to five saccharides. Studies of urine samples collected from several individuals indicated the common occurrence of these inhibitory alpha-mannosides. Type 1 fimbriae bound to immobilized T-H glycoprotein, but, unlike S fimbriae, their binding was poorly inhibited by soluble T-H glycoprotein. Some urine samples were also found to contain low-molecular-weight inhibitors for the O75X adhesin of E. coli. These results emphasize that to function as a virulence factor in human urinary tract infections, an adhesin must evidently recognize such receptor structures at the infection sites that are not excreted in soluble form in urine. This prerequisite is filled by P fimbriae but not by type 1 or S fimbriae.
D018830:Adhesins, Escherichia coli; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006384:Hemagglutination; D006801:Humans; D008970:Molecular Weight; D009088:Mucoproteins / Q000378:metabolism*; D011485:Protein Binding; D014556:Urine / Q000382:microbiology*; D058949:Uromodulin
D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin