Unmasking pathogen traits for chronic colonization in neurogenic bladder
Seth A Reasoner1, Brendan T Frainey2, Owen F Hale3
1Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell Reports
|April 23, 2026
Summary
Children with spina bifida experience frequent urinary tract infections due to neurogenic bladder. Bacterial adaptation, not antibiotic resistance, drives chronic infections by enabling immune evasion.
Area of Science:
- Microbiology
- Genetics
- Pediatrics
Background:
- Neurogenic bladder, often caused by spina bifida, leads to recurrent bacterial colonization and urinary tract infections (UTIs).
- Understanding the evolutionary dynamics of the urinary microbiota in this population is crucial for managing chronic infections.
Purpose of the Study:
- To characterize the longitudinal changes in the urine microbiota of individuals with spina bifida.
- To investigate bacterial adaptation mechanisms contributing to chronic colonization and UTIs.
Main Methods:
- Established a longitudinal cohort of 77 children and young adults with spina bifida.
- Employed enhanced urine culture, 16S rRNA sequencing, and whole-genome sequencing of bacterial isolates.
- Analyzed historical isolates from a biobank for 5-year evolutionary comparisons.
Main Results:
- Identified high abundance of pathogens like E. coli and Klebsiella in urine samples.
- Observed two distinct patterns: rapid strain cycling post-antibiotics or single-strain persistence.
- Found that mutations in cell envelope genes, not antibiotic resistance, mediated immune evasion and altered phage susceptibility.
Conclusions:
- Bacterial adaptation, specifically through mutations in cell envelope genes, facilitates immune evasion and niche adaptation in the bladder.
- These adaptations, rather than increased antibiotic resistance, are key mechanisms driving chronic infections in neurogenic bladder.
- The study highlights fitness trade-offs in bacterial evolution within the urinary tract, providing a foundation for identifying novel therapeutic targets.
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