Research in the lab is focused on the pathogenesis of Escherichia coli urinary tract infections (UTIs), especially how probiotic or resident vaginal lactobacilli help protect against these infections and the role of caveolae and glycosphingolipids (GSLs) in UTI. Since the vaginal epithelium is a key staging area for uropathogenic E. coli, which colonize this mucosa and the periurethra prior to causing UTI, one area of investigation is vaginal physiology at baseline and near the time of UTI. We are conducting a clinical study of a probiotic lactobacillus in preventing UTI among healthy pre-menopausal women. Related lab studies include the roles of resident commensal and probiotic lactobacilli in the pathogenesis of UTI, using a model of cultured primary vaginal epithelial cells, also developed in the lab, as well as clinical and probiotic Lactobacillus isolates and clinical measures in the probiotic trial. We are also studying how E. coli invade bladder epithelium via caveolae, using a model of cultured primary bladder epithelium developed in the lab and characterized with respect to GSLs.
Other projects include:
We collaborate with several University of Washington colleagues including Drs. Steve Moseley, David Fredricks, Delia Scholes, and Tom Hawn. Outside the University, we work with Drs. Anthony Atala, Wake Forest University; Thomas ("Mac") Hooton, University of Miami; Harry Mobley, University of Michigan; and Soman Abraham, Duke University.
Hooton TM, Roberts PL, Stapleton AE. Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: A randomized trial. JAMA; 2012;307:583-9.
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Stapleton AE, Dziura D, Hooton TM, Cox M Yarova-Yarovaya Y, Chen S, Gupta K. Recurrent UTI and urinary E. coli in a randomized controlled trial of cranberry juice. Mayo Clinic Proceedings; 2012;87:143-50.
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Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, Yarova-Yarovaya Y, Fiedler T, Cox M, Stamm WE. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis 2011; 52:1212-7. Epub 2011 Apr 14.
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Vigil PD, Stapleton AE, Johnson JR, Hooton TM, Hodges AP, He Y, and Mobley HLT. Presence of putative repeat-in-toxin (RTX) gene tosA of Escherichia coli predicts successful colonization of the urinary tract. mBio 2011 May 3;2(3). pii: e00066-11. doi: 10.1128/mBio.00066-11. Print 2011.
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5. Spurbeck RR, Stapleton AE, Johnson JR, Walk ST, Hooton TM, Mobley HL. Fimbrial profiles predict virulence of uropathogenic Escherichia coli strains: contribution of ygi and yad fimbriae. Infect Immun. 2011;79:4753-63. Epub 2011 Sep 12.
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