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.