Urinary tract infections (UTIs) are the most frequent of kidney/urologic disease and a significant cause of morbidity and mortality. A critical event in ascending UTIs in women is colonization of the vaginal mucosa with fecal bacteria. Colonization is initiated by adherence which fluctuates and is influenced by mucosal cell surface and fluid characteristics and bacterial virulence. Susceptibility to UTIs is associated with Lewis (Le) blood group phenotypes which are determinants of the membrane structure of urogenital epithelial cells and which thus may influence their receptivity for uropathogens. The long term goal of this proposal is to identify and characterize host and bacterial factors that increase susceptibility to and the effects of UTIs. The association between susceptibility to UTIs and the Lewis phenotype will be studied by evaluating urogenital cell and mucous blood group antigens, cell adhesive characteristics and bacterial virulence determinants.
The specific aims are to determine the: 1. Relation between susceptibility to UTIs, the Lewis blood group phenotype and blood group antigen expression in women. Epithelial cells and mucous from the vaginal and buccal (control) mucosa will be assayed for H, A, B, Lea, Leb, Lex and Ley antigens using monoclonal antibodies in particle concentration fluorescence and ELISA assays. 2. Changes in expression of vaginal cell and mucous blood group antigens related to susceptibility to UTIs, the Lewis phenotype and changes in vaginal cell receptivity. a) Women with recurrent UTIs and controls will be Lewis phenotyped and expression of blood group antigens on their vaginal cells (and mucous) will be measured biweekly for 6 months to assess intra- subject variation. b) The receptivity of the vaginal cells for E. coli strains expressing Type 1 or P adhesins will be determined in adherence assays. 3. Relationship of the Lewis blood group phenotype and uroepithelial cell blood group antigens with bacterial adhesins and other virulence determinants. E. coli isolates from women with known Lewis phenotypes and uroepithelial cell blood group antigens will be collected and assayed for expression of adhesion (Type 1, P, S), production of hemolysin and resistance to serum bactericidal activity. It is hypothesized that increased susceptibility to UT s in women with Le(a+b-) and Le(a-b-) phenotypes is directly associated with less frequent and/or intense expression of vaginal cell and/or mucous blood group antigens, increased epithelial cell receptivity, and infection with less virulent E. coli.
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