Stapleton A E, Stroud M R, Hakomori S I, Stamm W E
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
Infect Immun. 1998 Aug;66(8):3856-61. doi: 10.1128/IAI.66.8.3856-3861.1998.
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 35S labeled these five E. coli isolates and measured their relative binding affinities to serial dilutions of SGG and DSGG as well as to globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4), 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, Gb3, and Gb4, 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.
有复发性大肠杆菌尿路感染（UTI）病史的女性相比没有此类病史的女性，更有可能是血型抗原的非分泌者，并且非分泌者的阴道上皮细胞（VEC）与分泌者的细胞相比，显示出尿路致病性大肠杆菌分离株的黏附增强。我们之前从天然VEC中提取了糖鞘脂（GSLs），并确定非分泌者（而非分泌者）选择性表达两种延长的球系列GSLs，唾液酸基半乳糖基球蛋白苷（SGG）和二唾液酸基半乳糖基球蛋白苷（DSGG），它们特异性结合表达P菌毛黏附素的尿路致病性大肠杆菌R45。在本研究中，我们通过从该来源纯化化合物，证明SGG和DSGG在人肾组织中表达。我们还证明，从人肾中分离的SGG和DSGG结合表达三类pap编码黏附素中每一类的尿路致病性大肠杆菌分离株，包括表达来自J96的PapG、来自J96的PrsG和来自IA2的PapG的克隆分离株，以及野生型分离株IA2和R45。我们用35S对这五种大肠杆菌分离株进行代谢标记，并测量它们对SGG和DSGG系列稀释液以及对泌尿生殖组织中存在的另外两种球系列GSLs，球三糖神经酰胺（Gb3）和球四糖神经酰胺（Gb4）的相对结合亲和力。与它们与DSGG、Gb3和Gb4的结合相比，这五种大肠杆菌分离株中的每一种与SGG的结合亲和力最高，并且每种分离株都有独特的GSL结合亲和力模式。这些研究进一步表明，SGG可能在UTI的发病机制中起重要作用，并且它可能是大肠杆菌与非分泌者的尿道上皮细胞结合增加以及非分泌者对复发性UTI易感性增加的原因。
