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

Nicole J. De Nisco, Michael Neugent, Jason A Mull, Luming Chen, Amy Kuprasertkul, Marcela de Souza Santos, Kelli L. Palmer, Philippe E Zimmern, Kim A Orth

Research output: Contribution to journalArticle

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Abstract

Urinary 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.

Original languageEnglish (US)
JournalJournal of Molecular Biology
DOIs
StatePublished - Jan 1 2019

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Urinary Tract Infections
Urinary Bladder
Urothelium
Inflammation
Bacteria
Adaptive Immunity
Anti-Bacterial Agents
Biopsy
Cystoscopy
Mesoderm
Plasma Cells
Edema
B-Lymphocytes
Therapeutics
Quality of Life
Urine
Lymphocytes
Delivery of Health Care
Recurrence
Infection

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection. / De Nisco, Nicole J.; Neugent, Michael; Mull, Jason A; Chen, Luming; Kuprasertkul, Amy; de Souza Santos, Marcela; Palmer, Kelli L.; Zimmern, Philippe E; Orth, Kim A.

In: Journal of Molecular Biology, 01.01.2019.

Research output: Contribution to journalArticle

De Nisco, Nicole J. ; Neugent, Michael ; Mull, Jason A ; Chen, Luming ; Kuprasertkul, Amy ; de Souza Santos, Marcela ; Palmer, Kelli L. ; Zimmern, Philippe E ; Orth, Kim A. / Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection. In: Journal of Molecular Biology. 2019.
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