An estimated 150 million UTIs occur annually on a global basis, accounting for direct health care costs of $6 billion. While no aggregate assessment of the morbidity, mortality and total costs related to UTIs can be calculated, these infections clearly represent a significant public health burden. This program project proposes studies that will improve our understanding of the epidemiology , risk factors, microbial ecology, molecular pathogenesis and prevention of UTIs. The objectives of the project will be met through the development of a multi-disciplinary research team that will collaborate to carry out four interrelated projects. Project 1 will delineate the protective role of hydrogen peroxide producing lactobacilli, the major microbial species of the normal vaginal flora, in preventing vaginal colonization with E. coli and UTI in young women. The project will ultimately test a novel approach to the prevention of UTI in women, namely, use of a highly adherent hydrogen peroxide producing lactobacillus strain administered as a vaginal suppository. In Project 2, the role and regulation of bladder epithelial cell glycosphingolipids as attachment sites for uropathogenic bacteria will be studied using primary cultures of bladder epithelial cells. Identification of specific interactions between bacterial adhesins and epithelial cell glycosphingolipid receptors may facilitate the development of novel means of prevention using topically applied comparative analogs. Project 3 will identify new virulence genes in two important uropathogens, E. coli and Pseudomonas aeruginosa by studying gene expression under conditions of actual infection. In Project 4, the epithelial cell responses and intracellular signaling pathways that are activated after Dr fimbria bearing E. coli attach to epithelial cells via Decay Accelerating Factor will be studied. A laboratory core will provide primary bladder epithelial cells, ribotyping, characterization of urovirulence genes and other resources to the projects. An Administrative/Biostatistical Core will coordinate the project and provide biostatistical expertise to project investigators. The proposed studies will result in new approaches to the prevention of UTIs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK053369-01
Application #
2450678
Study Section
Special Emphasis Panel (ZDK1-GRB-B (O1))
Project Start
1998-02-24
Project End
2003-01-31
Budget Start
1998-02-24
Budget End
1999-01-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Stapleton, Ann E (2013) Cranberry-containing products are associated with a protective effect against urinary tract infections. Evid Based Med 18:110-1
Hooton, Thomas M; Roberts, Pacita L; Cox, Marsha E et al. (2013) Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med 369:1883-91
Bateman, Stacey L; Stapleton, Ann E; Stamm, Walter E et al. (2013) The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli. Microbiology 159:1606-17
Stapleton, Ann E; Dziura, James; Hooton, Thomas M et al. (2012) Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial. Mayo Clin Proc 87:143-50
Chaturvedi, Kaveri S; Hung, Chia S; Crowley, Jan R et al. (2012) The siderophore yersiniabactin binds copper to protect pathogens during infection. Nat Chem Biol 8:731-6
Hooton, Thomas M; Roberts, Pacita L; Stapleton, Ann E (2012) Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial. JAMA 307:583-9
Spurbeck, Rachel R; Dinh Jr, Paul C; Walk, Seth T et al. (2012) Escherichia coli isolates that carry vat, fyuA, chuA, and yfcV efficiently colonize the urinary tract. Infect Immun 80:4115-22
Vigil, Patrick D; Stapleton, Ann E; Johnson, James R et al. (2011) Presence of putative repeat-in-toxin gene tosA in Escherichia coli predicts successful colonization of the urinary tract. MBio 2:e00066-11
Spurbeck, Rachel R; Stapleton, Ann E; Johnson, James R et al. (2011) Fimbrial profiles predict virulence of uropathogenic Escherichia coli strains: contribution of ygi and yad fimbriae. Infect Immun 79:4753-63

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