Variation of high mannose chains of Tamm-Horsfall glycoprotein confers differential binding to type 1-fimbriated Escherichia coli.
Tamm-Horsfall glycoprotein (THP), the most abundant protein in mammalian urine, has been implicated in defending the urinary tract against infections by type 1-fimbriated Escherichia coli. Recent experimental evidence indicates that the defensive capability of THP relies on its single high mannose chain, which binds to E. coli FimH lectin and competes with mannosylated uroplakin receptors on the bladder surface. Here we describe several major differences, on both structural and functional levels, between human THP (hTHP) and pig THP (pTHP). pTHP contains a much higher proportion (47%) of Man5GlcNAc2 than does hTHP (8%). FimH-expressing E. coli adhere to monomeric pTHP at an approximately 3-fold higher level than to monomeric hTHP. This suggests that the shorter high mannose chain (Man5GlcNAc2) is a much better binder for FimH than the longer chains (Man6-7GlcNAc2) and that pTHP is a more potent urinary defense factor than hTHP. In addition, unlike hTHP whose polyantennary glycans are exclusively capped by sialic acid and sulfate groups, those of pTHP are also terminated by Galalpha1,3Gal epitope. This is consistent with the fact that the outer medulla of pig kidney expresses the alpha1,3-galactosyltransferase, which is completely absent in human kidney. Finally, pTHP is more resistant to leukocyte elastase hydrolysis than hTHP, thus explaining why pTHP is much less prone to urinary degradation than hTHP. These results demonstrate for the first time that the species variations of the glycomoiety of THP can lead to the differential binding of THP to type 1-fimbriated E. coli and that the differences in high mannose processing may reflect species-specific adaptation of urinary defenses against E. coli infections.
Department of Experimental Pathology, University of Bologna, Bologna 40126, Italy.
Daniela
D
Cavallone
Nadia
N
Malagolini
Angela
A
Monti
Xue-Ru
XR
Wu
Franca
F
Serafini-Cessi
D000818:Animals; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D004926:Escherichia coli / Q000648:ultrastructure*; D010861:Fimbriae, Bacterial / Q000502:physiology*; D006020:Glycopeptides / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007668:Kidney / Q000502:physiology; D008358:Mannose / Q000032:analysis*; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D012016:Reference Values; D013045:Species Specificity; D013552:Swine; D058949:Uromodulin
D006020:Glycopeptides; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D008358:Mannose