Detection of intracellular bacterial communities in human urinary tract infection
David A Rosen1, Thomas M Hooton, Walter E Stamm
1Department of Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, Missouri, United States of America.
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.
Insights
Intracellular bacterial communities (IBCs) and filamentous bacteria, previously seen in mice, were found in the urine of women with urinary tract infections (UTIs). This suggests a similar infection pathway may occur in humans, impacting UTI recurrence and treatment.
Area of Science:
- Microbiology
- Urology
- Infectious Diseases
Background:
- Urinary tract infections (UTIs) are common bacterial infections, often caused by uropathogenic Escherichia coli (UPEC).
- Recent studies show UPEC can form intracellular bacterial communities (IBCs) within the bladder urothelium in mice, leading to recurrent infections.
- The occurrence of this IBC pathway in humans has not been previously investigated.
Purpose of the Study:
- To investigate the presence of the IBC pathogenic pathway in urine samples from women experiencing acute UTIs.
- To determine if evidence of intracellular bacterial communities and filamentous bacteria can be detected in human UTI cases.
Main Methods:
- Urine specimens were collected from 80 women with acute cystitis and 20 asymptomatic women.
- Samples were analyzed using light microscopy, immunofluorescence, and electron microscopy.
- Investigators were blinded to clinical history and culture results.
Main Results:
- Evidence of exfoliated IBCs was found in 18% of women with UTIs, compared to none in the asymptomatic group.
- Filamentous bacteria were observed in 41% of UTI cases and were significantly associated with the presence of IBCs (p < 0.001).
- IBCs and filamentous bacteria were primarily associated with E. coli infections, not gram-positive infections.
Conclusions:
- The detection of IBCs and filamentous bacteria in human urine suggests the IBC pathogenic pathway may occur in women with UTIs.
- These findings support the existence of an intracellular bacterial niche in some human UTIs.
- This intracellular pathway has potential implications for understanding and treating recurrent UTIs.
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