Women with a history of recurrent Escherichia coli urinary tract infections (UTIs) are significantly more likely to be nonsecretors of blood group antigens than are women without such a history, and vaginal epithelial cells (VEC) from women who are nonsecretors show enhanced adherence of uropathogenic E. coli isolates compared with cells from secretors. We previously extracted glycosphingolipids (GSLs) from native VEC and determined that nonsecretors (but not secretors) selectively express 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 demonstrated, 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 isolates expressing each of the three classes of pap-encoded adhesins, including cloned isolates expressing PapG from J96, PrsG from J96, and PapG from IA2, and the wild-type isolates IA2 and R45. We metabolically 35 S labeled these five E. coli 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 compared with their binding to DSGG, Gb 3 , and Gb 4 , and each isolate had a unique pattern of GSL binding affinity. These studies further suggest that SGG likely plays an important role in the pathogenesis of UTI and that its presence may account for the increased binding of E. coli to uroepithelial cells from nonsecretors and for the increased susceptibility of nonsecretors to recurrent UTI.Several epidemiological studies have shown that women who are nonsecretors of blood group antigens have a three-to fourfold-increased risk of developing recurrent urinary tract infection (UTI) (5,17,32). In addition, uroepithelial cells from nonsecretors have a two-to threefold-greater capacity for adherence of uropathogenic Escherichia coli than do cells from secretors (22). Colonization of the vaginal and periurethral epithelium precedes the development of E. coli UTI, and E. coli isolates expressing pap-encoded adhesins are overrepresented among isolates causing these infections (6). Uropathogenic E. coli isolates expressing pap-encoded adhesins bind to globoseries glycosphingolipids (GSLs) (6, 19), which are amphipathic molecules embedded in the outer leaflets of eukaryotic cell membranes. There are several families of GSLs which are differentiated by their molecular structures, and these molecules serve as bacterial and viral adhesion sites on mammalian cells and as markers of eukaryotic cell differentiation and oncogenesis (4).In previous investigations, we collected vaginal epithelial cells from secretors and nonsecretors and extracted the GSLs from pooled cells from women in eac...