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Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection
Open accessAbstract
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 [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]
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Ambite, I., Nagy, K., Godaly, G., Puthia, M., Wullt, B., & Svanborg, C. (2016) · ASM Press eBooks · doi:10.1128/9781555817404.ch21 · Cited by 3
Introduction to biofilms in urology
Cadieux, P. A., Wignall, G. R., & Carriveau, R. (2009) · Elsevier eBooks · doi:10.1533/9781845696375.1.3 · Cited by 3
The role of oxidative stress in pediatric urinary tract infections: a systematic review
Delshad, M., Fesharakinia, A., & Eghbal, S. (2016) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.17463/rcm.2016.01.010 · Cited by 3
“urinary tract infections are usually caused by a variety of bacteria, especially gram-negative bacteria such as Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and different types of fungi and viruses (1,2).”
BackgroundFrequent Urinary Tract Infection
Turpen, H. C. (2017) · Physician Assistant Clinics · doi:10.1016/j.cpha.2017.08.007 · Cited by 3
Patel, R. S., Christie, A. L., & Zimmern, P. E. (2023) · Urological Science · doi:10.4103/uros.uros_74_22 · Cited by 3
Bacterial infections of the urinary tract
Same, R. G., & Hunstad, D. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-79525-8.00019-6 · Cited by 3
The role of bacterial virulence factors in the clinical course of urinary tract infections
Köves, B. (2014) · doi:10.14232/phd.2231 · Cited by 3
E. coli division machinery drives cocci development inside host cellsPreprint
Pokhrel, A., Costas, A., Pittorino, M. J., Duggin, I. G., & Söderström, B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.08.588611 · Cited by 3
Jariah, R. O. A., Schofield, J., West, K., Michniewski, S., Jameson, E., Onions, L., Saravanan, A., Yeşilkaya, H., Millard, A. D., Clokie, M. R. J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.01.646603 · Cited by 3
Hagan, E. C. (2009) · Deep Blue (University of Michigan) · Cited by 3
Cranberry constituents prevent SOS-mediated filamentation of uropathogenic Escherichia coli
Prinster, T., Harrison, A., Dick, C., Horvath, D., Li, B.-R., Sievers, G., Madamsetty, R., Zhang, J., Mason, K. M., Khoo, C., et al. (2025) · Infection and Immunity · doi:10.1128/iai.00600-24 · Cited by 3
“Filamentous morphotypes are readily observed in urine samples obtained from patients who suffer from UTI caused by UPEC, Klebsiella pneumoniae , Enterobacter aerogenes , and Proteus mirabilis (53).”
Piedad, J. C. P., & Yang, B. (2025) · Future Microbiology · doi:10.1080/17460913.2025.2503695 · Cited by 2
Uropathogenic Escherichia coli proliferate as a coccoid morphotype inside human host cells
Pokhrel, A., Chisholm, L., Costas, A., Pittorino, M. J., Duggin, I. G., & Söderström, B. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003366 · Cited by 2
Manoharan, A., Wijekoon, N., Whiteley, G. S., Ashishkumar, T. D., Rodriguez, N. F., Jensen, S. O., Söderström, B., Moore, K. H., Manos, J., Marais, B. J., et al. (2025) · ASM Case Reports · doi:10.1128/asmcr.00077-25 · Cited by 2
Harding, C., Silva, A. S. D., Khasriya, R., Khullar, V., Lombardo, R., Malde, S., Nambiar, A., Rademakers, K. L. J., & Werneburg, G. T. (2025) · Neurourology and Urodynamics · doi:10.1002/nau.70200 · Cited by 2
“Contemporary research suggests that CUTI involves complex bacterial behaviour previously not well understood [33–35].”
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Joshi, B., Zulk, J. J., Serchejian, C., Hameed, Z. A., Larson, A. B., Terwilliger, A. L., Kumar, D., Mysorekar, I. U., Britton, R. A., Maresso, A. W., et al. (2026) · Infection and Immunity · doi:10.1128/iai.00543-25 · Cited by 2
“Along with antibiotic resistance, UPEC undermines antibiotic efficacy by establishing intracellular bacterial communities within the bladder (34, 35) and the vaginal epithelium (36), which are protected from antibiotic therapy and could serve as an additional source of recurrent infection (37).”
N-(pyridin-4-yl)benzo[d]thiazole-6-carboxamide inhibits E. coli UT189 bacterial capsule biogenesis
Noah, J. W., Ananthan, S., Evans, C. W., Nebane, N. M., Rasmussen, L. A., Sosa, M. I., Tower, N. A., White, E. L., Seed, P. C., Goller, C., et al. (2013) · Europe PMC (PubMed Central) · Cited by 2
Pathogenic Biofilms as Triggers of Recurrent Vaginitis and Cystitis
Graziottin, A., & Resnati, H. S. R. (2015) · Cited by 2
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Reyes-Gualito, A., Macías, A. E., Reyes‐Escogido, M. D. L., Mendoza-Macías, C. L., & Alvarez, J. A. (2023) · American Journal of Infection Control · doi:10.1016/j.ajic.2023.08.016 · Cited by 2
Immunity to urinary tract infection: What the clinician should know
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Innovative Solutions to Sticky Situations: Antiadhesive Strategies for Treating Bacterial Infections
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Metadata
- 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 › Urology › Urinary Tract Infections Management
- Life Sciences › Immunology and Microbiology › Microbiology › 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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