A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.
Carlos FloresJefferson LingAmanda LohRamón Garcia MasetAngeline AwIan J WhiteRaymond FernandoJennifer L RohnPublished in: Science advances (2023)
Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli , suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus . Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level.
Keyphrases
- escherichia coli
- urinary tract infection
- endothelial cells
- biofilm formation
- high grade
- induced apoptosis
- urinary tract
- pseudomonas aeruginosa
- induced pluripotent stem cells
- staphylococcus aureus
- pluripotent stem cells
- cell cycle arrest
- immune response
- gram negative
- high glucose
- cell migration
- stem cells
- high resolution
- cell death
- multidrug resistant
- diabetic rats
- liquid chromatography