Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

Abstract

We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro. Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni <i>t</i>-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation. All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (<i>Escherichia/Shigella, Pseudomonas, Staphylococcus</i>, <i>Ureaplasma</i>) and in those associated with infection (<i>Escherichia/Shigella</i>, <i>Ureaplasma</i>). The enriched interaction subnetwork in stent-associated infection included <i>Ureaplasma</i> and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (<i>Enterococcus faecalis</i> most) and material type (titanium least). Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.