LB-S&T-35 SIDEROPHORE VACCINE CONJUGATES PROTECT AGAINST UROPATHOGENIC ESCHERICHIA COLI IN A MURINE MODEL OF URINARY TRACT INFECTION

Abstract

You have accessJournal of UrologyLate-Breaking S&T Poster1 Apr 2016LB-S&T-35 SIDEROPHORE VACCINE CONJUGATES PROTECT AGAINST UROPATHOGENIC ESCHERICHIA COLI IN A MURINE MODEL OF URINARY TRACT INFECTION Laura Mike, Sara Smith, Christopher Sumner, and Harry Mobley Laura MikeLaura Mike More articles by this author , Sara SmithSara Smith More articles by this author , Christopher SumnerChristopher Sumner More articles by this author , and Harry MobleyHarry Mobley More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.03.116AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of uncomplicated urinary tract infections (UTIs). Over half of all women will experience a UTI in their lifetime and one in forty women suffers recurrent UTIs. The repeated administration of antibiotics to treat recurrent UTIs has resulted in a steady increase in antibiotic resistance among UPEC isolates. The objective of this study was to identify novel vaccine strategies for the prevention of UTIs. Bacteria-derived siderophores, which are secreted small molecules used for iron acquisition, were targeted for use in our UTI vaccine. Specifically, the two siderophores aerobactin (Aebt) and yersiniabactin (Ybt) were selected due to their proven role in bacterial virulence, their association with pathogenic E. coli strains, their surface exposed nature, and the protection their cognate outer membrane protein receptors provide against experimental UTI. METHODS Aebt and Ybt were conjugated to immunogenic cationized bovine serum albumin (cBSA). Mice were intranasally vaccinated with cBSA, cBSA conjugated to Aebt (cBSA-Aebt), cBSA conjugated to Ybt (cBSA-Ybt), or a mixture of the two antigen conjugates. After the initial vaccination, mice were boosted once a week for two weeks. Mice were then intraurethrally challenged with UPEC. Bacterial burdens in the urine, bladder, and kidneys were quantified after 48 hours of infection. RESULTS Vaccination with cBSA-Aebt, cBSA-Ybt, or the 1:1 mixture of the two cBSA-conjugates resulted in a ten-fold decrease in bacterial burdens in the urine compared to mice vaccinated with cBSA alone. Mice vaccinated with cBSA-Ybt had a ten-fold decrease in bacterial burden in the kidneys. Combining the two vaccine conjugates resulted in a 100-fold decrease in bacterial burden in the kidneys. Further studies revealed that vaccination with these cBSA-siderophore conjugates stimulates an adaptive immune response that recognizes the bacterial siderophores. CONCLUSIONS The data presented here identify the potential use of bacterial siderophores in a UTI vaccine. This is the first evidence that bacteria-specific small molecules can be formulated into a protective vaccine and represent untapped resources as antigens in other bacterial diseases. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e351 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Laura Mike More articles by this author Sara Smith More articles by this author Christopher Sumner More articles by this author Harry Mobley More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...