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.
Cell reports. 2026 Apr 22 [Epub ahead of print]
Seth A Reasoner, Brendan T Frainey, Owen F Hale, Alexandra Borden, M Kyle Graham, Elise Turner, Lucas R Brenes, Carl B W Soderstrom, Hamilton Green, Jonathan E Schmitz, Michael T Laub, Maryellen S Kelly, Douglass B Clayton, Maria Hadjifrangiskou
Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Department of Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: ., Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA., Division of Pediatric Urology, Department of Urology, Duke Health, Durham, NC 27710, USA., Department of Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center for Personalized Microbiology (CPMi), Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology & Inflammation (VI4), Vanderbilt University Medical Center, Nashville, TN 37232, USA., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Division of Pediatric Urology, Department of Urology, Duke Health, Durham, NC 27710, USA; Division of Healthcare of Women and Children, School of Nursing, Duke University, Durham, NC 27710, USA., Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center for Personalized Microbiology (CPMi), Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology & Inflammation (VI4), Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: .