MP34-13 SYNERGY BETWEEN THE HOST IMMUNE SYSTEM AND BACTERIOPHAGES SUPPORTS PHAGE THERAPY FOR URINARY TRACT INFECTION

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP34-13 SYNERGY BETWEEN THE HOST IMMUNE SYSTEM AND BACTERIOPHAGES SUPPORTS PHAGE THERAPY FOR URINARY TRACT INFECTION Kathrin Bausch Kathrin BauschKathrin Bausch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003268.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract infections (UTI) are one of the most common bacterial infections affecting >150 million people world-wide, every year. Globally, extraintestinal pathogenic Escherichia coli (ExPEC), which include uropathogenic E. coli, increasingly display resistance to antibiotics. One ExPEC clonal group, sequence type 131 (ST131), has emerged as a pandemic multidrug-resistant pathogen. To continue to be able to effectively treat UTI, despite increasing rates of antibiotic resistance, bacteriophage therapy is attracting renewed interest. Although phage therapy has been used for decades, mechanisms underlying phage-mediated bacterial clearance in UTI remain largely unknown. METHODS: To address this question, we investigated phage treatment for UTI caused by the ST131 strain JJ2528 and its effects on the bladder immune response in a mouse model. RESULTS: Using this model, we found that female C57BL/6 mice infected with JJ2528 had significantly reduced bladder bacterial burdens compared to untreated mice when they received phage HP3 either intraperitoneally or intravesically. Additionally, we found phage therapy may protect memory responses. Our previous work demonstrates that a non-sterilizing adaptive immune response arises following an acute UTI, but elimination of bacteria by antibiotics ablates development of immune memory. We tested whether phage-treated mice, in which bacteria are cleared from the bladder with a similar kinetic to antibiotic treatment, had an impaired memory response. Surprisingly, bacterial burden in challenged animals was similar between control and phage-treated animals, suggesting that immune memory is intact. While bacteriophage therapy alone did not induce inflammation in the bladder, phage therapy in the context of infection induced a significant increase in neutrophil infiltration compared to control-treated mice. To determine the role of neutrophils in phage treatment, we used two models of neutrophil depletion and treated infected mice with phages. Neutrophil-depleted mice had a significantly higher bacterial burden compared to non-depleted mice, supporting that neutrophil infiltration is necessary for phage treatment efficacy. A possible mechanism behind this may be that the administration of phages and bacteria leads to increased ROS production and cell death in human neutrophils compared to bacteria alone. CONCLUSIONS: Our data demonstrate that phage treatment is effective in reducing a primary UTI and does not impair the development of immune memory to rUTI. Phage treatment induces a neutrophil infiltration that is essential for phage efficacy mediated by increased ROS production and “cell death”. This study supports that phage treatment of UTI is a potentially viable alternative to antibiotics for this very common infection. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e464 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathrin Bausch More articles by this author Expand All Advertisement PDF downloadLoading ...