Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection
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BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. METHODS AND FINDINGS: We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. CONCLUSIONS: The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.
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IBCs have long been reported in the urine of patients with acute cystitis; however, they have not been detected in the urine of patients with acute episodes of rUTIs.
“IBCs have long been reported in the urine of patients with acute cystitis; however, they have not been detected in the urine of patients with acute episodes of rUTIs [25].”
From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [25]
The Results (Comparison of Cystitis and Asymptomatic Subjects; page not available) report IBCs in 14 of 80 urine specimens from women with acute cystitis. The Discussion says the patients were not followed prospectively, so the study could not evaluate patterns of recurrence. It does not establish that IBCs have not been detected during acute episodes of recurrent UTI. (LLM, conf=0.89)
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- Authors
- Rosen, D. A., Hooton, T. M., Stamm, W. E., Humphrey, P. A., & Hultgren, S. J.
- Affiliations
- Washington University in St. Louis (US)
- University of Miami (US)
- University of Washington (US)
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-12-18
- Volume
- 4
- Issue
- 12
- Pages
- e329
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC2140087
- OpenAlex
- W2118051267
- Cited by
- 651
- References
- 31
- Citations by year
- 2026: 28 · 2025: 33 · 2024: 40 · 2023: 35 · 2022: 35 · 2021: 41 · 2020: 36 · 2019: 36 · 2018: 23 · 2017: 42 · 2016: 55 · 2015: 37 · 2014: 39 · 2013: 42 · 2012: 29
- FWCI
- 16.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Washington
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK053369, DK-53369, R01 DK64540, P50DK064540, DK051406, P01 DK53369, DK64540, R01DK051406)
- Office of Research on Women's Health
- Topics
- Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- urinary tract infection, intracellular bacterial communities, uropathogenic Escherichia coli, acute uncomplicated cystitis, filamentous bacteria, recurrent urinary tract infection, women, bladder urothelium, human urine
- MeSH terms
- Acute Disease, Adult, Animals, Bacteria, Urinary Bladder, Cystitis, Disease Models, Animal, Escherichia coli Infections, Female, Fluorescent Antibody Technique, Humans, Mice, Inbred C3H, Microscopy, Electron, Scanning, Middle Aged, Recurrence, Urinary Tract Infections, Urine, Case-Control Studies, Urothelium, Mice
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