Unmasking pathogen traits for chronic colonization in neurogenic bladder
Individuals with neurogenic bladder are susceptible to chronic bacterial colonization and urinary tract infections. Neurogenic bladder arises from conditions including spinal cord injuries and spina bifida. We established a longitudinal cohort of 77 children and young adults with spina bifida. Using enhanced urine culture, 16S rRNA sequencing, and whole-genome sequencing of bacterial isolates, we characterized the urine microbiota. We also retrieved prior bacterial isolates from Vanderbilt's MicroVU biobank, enabling 5-year evolutionary comparisons within subjects. Urine samples showed high abundance of pathogens, including E. coli and Klebsiella. Across time points, subjects exhibited either rapid cycling of strains, often after antibiotics, or persistence of a single strain. Neither pattern consistently correlated with increased antibiotic resistance. Instead, mutations in cell envelope genes mediated immune evasion and altered phage susceptibility, highlighting fitness trade-offs induced by niche adaptation to the bladder. This cohort enables the identification of bacterial adaptation mechanisms.
Authors
- Douglass B. Clayton (ORCID: https://orcid.org/0000-0003-4460-4167)
- Jonathan E. Schmitz (ORCID: https://orcid.org/0000-0002-2727-9078)
- Carl A. Soderstrom
- Maria Hadjifrangiskou (ORCID: https://orcid.org/0000-0003-4249-8997)
- Kyle Graham (ORCID: https://orcid.org/0000-0001-7664-6703)
- Hamilton Green
- Maryellen S. Kelly (ORCID: https://orcid.org/0000-0001-7733-8569)
- Owen F. Hale (ORCID: https://orcid.org/0000-0003-3895-1357)
- Michael T. Laub (ORCID: https://orcid.org/0000-0002-8288-7607)
- Seth A. Reasoner (ORCID: https://orcid.org/0000-0002-7791-1641)
- Brendan T. Frainey (ORCID: https://orcid.org/0000-0003-0371-7122)
- Lucas R. Brenes
- Elise H. Turner
- Alexandra Borden
Institutions
- Howard Hughes Medical Institute (US)
- Duke University (US)
- Vanderbilt University (US)
- Duke Children's Hospital & Health Center (US)
- Duke University Health System (US)
- Massachusetts Institute of Technology (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-04-22
- DOI
- https://doi.org/10.1016/j.celrep.2026.117302
- Primary Topic
- Urinary Tract Infections Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Vanderbilt University Medical Center
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases