Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection

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dc.contributor.ORCID0000-0002-7343-9271 (Palmer, KL)
dc.contributor.authorDe Nisco, N. J.
dc.contributor.authorNeugent, Michael
dc.contributor.authorMull, J.
dc.contributor.authorChen, L.
dc.contributor.authorKuprasertkul, A.
dc.contributor.authorde Souza Santos, M.
dc.contributor.authorPalmer, Kelli L.
dc.contributor.authorZimmern, P.
dc.contributor.authorOrth, K.
dc.contributor.utdAuthorNeugent, Michael
dc.contributor.utdAuthorPalmer, Kelli L.
dc.date.accessioned2020-02-06T23:00:12Z
dc.date.available2020-02-06T23:00:12Z
dc.date.created201904-17
dc.descriptionDue to copyright restrictions full text access from Treasures at UT Dallas is restricted to current UTD affiliates (use the provided Link to Article).
dc.descriptionIncludes supplementary information
dc.description.abstractUrinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. The molecular basis of RUTI, especially in postmenopausal women, has remained unclear because modeling RUTI in mice is difficult, and human data are limited. Invasion of the urothelium and induction of host inflammation are hypothesized to be key mechanisms by which bacterial pathogens cause RUTI. To further our understanding of RUTI in humans, we performed a systematic analysis of urine and bladder biopsy samples from postmenopausal women undergoing cystoscopy with fulguration of trigonitis in the advanced management of antibiotic-refractory RUTI. We provide direct evidence that bacteria reside in the bladder wall of postmenopausal RUTI patients and that diverse bacterial species can be isolated from the bladder tissue. Histopathological scoring revealed significant edema and alterations of urothelial architecture in RUTI patient biopsies. Lymphocytes, including plasma B-cells, were detected within the mesenchyme, urothelium, and follicular aggregates in the majority of patients, indicating that the local adaptive immune response is active during human RUTI. These data provide conclusive evidence that bacteria invade the human urothelium and suggest that diverse bacterial species and the adaptive immune response play important roles in RUTI in humans. © 2019 Elsevier Ltd
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.sponsorshipNational Institutes of Health (NIH; grants R01-AI056404 and R01 GM115188) and the Welch Foundation (grant I-1561).
dc.identifier.bibliographicCitationDe Nisco, N. J., M. Neugent, J. Mull, L. Chen, et al. 2019. "Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection." Journal of Molecular Biology 431: 4368-4379, doi: 10.1016/j.jmb.2019.04.008
dc.identifier.issn0022-2836
dc.identifier.urihttp://dx.doi.org/10.1016/j.jmb.2019.04.008
dc.identifier.urihttps://hdl.handle.net/10735.1/7247
dc.identifier.volume431
dc.language.isoen
dc.publisherAcademic Press
dc.rights©2019 Elsevier Ltd. All Rights Reserved.
dc.source.journalJournal of Molecular Biology
dc.subjectUrinary tract infections, Recurrent
dc.subjectWomen (Postmenopausal)
dc.subjectEdema
dc.subjectBladder--Diseases
dc.subjectLymphocytes
dc.titleDirect Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection
dc.type.genrearticle

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