THE GLOBOSERIES GLYCOSPHINGOLIPID SIALOSYL GALACTOSYL GLOBOSIDE IS FOUND IN URINARY-TRACT TISSUES AND IS A PREFERRED BINDING-RECEPTOR IN-VITRO FOR UROPATHOGENIC ESCHERICHIA-COLI EXPRESSING PAP-ENCODED ADHESINS

Women with a history of recurrent Escherichia coli urinary tract infec tions (UTIs) are significantly more likely to be nonsecretors of blood group antigens than are women without such a history, and vaginal epi thelial cells (VEC) from women who are nonsecretors show enhanced adhe rence of uropathogenic E. coli isolates compared with cells from secre tors, We previously extracted glycosphingolipids (GSLs) from native VE C and determined that nonsecretors (but not secretors) selectively exp ress two extended globoseries GSLs, sialosyl galactosyl globoside (SGG ) and disialosyl galactosyl globoside (DSGG), which specifically bound uropathogenic E. coli R45 expressing a P adhesin, In this study, we d emonstrated, by purifying the compounds from this source, that SGG and DSGG are expressed in human kidney tissue. We also demonstrated that SGG and DSGG isolated from human kidneys bind uropathogenic E. coli is olates expressing each of the three classes of pnp-encoded adhesins, i ncluding cloned isolates expressing PapG from J96, PrsG from J96, and PapG from IA2, and the wild-type isolates IA2 and R45, We metabolicall y S-35 labeled these five E. coil isolates and measured their relative binding affinities to serial dilutions of SGG and DSGG as well as to globotriaosylceramide (Gb(3)) and globotetraosylceramide (Gb(4)), two other globoseries GSLs present in urogenital tissues. Each of the five E, coli isolates bound to SGG with the highest apparent avidity compa red with their binding to DSGG, Gb(3), and Gb(4), and each isolate had a unique pattern of GSL binding affinity, These studies further sugge st that SGG likely plays an important role in the pathogenesis of UTI and that its presence may account for the increased binding off. coli to uroepithelial cells from nonsecretors and for the increased suscept ibility of nonsecretors to recurrent UTI.