A model of polymicrobial catheter-associated urinary tract infection reveals biofilm-mediated modulation of treatment efficacy

BACKGROUND: Catheter-associated urinary tract infections (CAUTI) are among the most prevalent healthcare-associated infections and an important site for development and spread of antimicrobial resistance. Although CAUTI are frequently polymicrobial, the majority of research focuses on individual pathogens in monoculture, largely due to a lack of representative and tractable models. AIMS: The aim of this study was to develop a tractable and reproducible model of polymicrobial CAUTI. METHODS: Here we describe the use of an in vitro model of the catheterized urinary tract to generate polymicrobial communities encompassing common uropathogens (Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Proteus mirabilis), in an environment representative of the catheterized urinary tract. RESULTS AND CONCLUSIONS: We show that our system establishes stable and reproducible polymicrobial communities and facilitates analysis across both planktonic and biofilm lifestyles. We confirm that polymicrobial biofilms in this system display distinct population dynamics compared to planktonic populations and modulate the impact of ciprofloxacin treatment by protecting the most susceptible community members. In addition, we demonstrate the capacity of P. mirabilis to encrust and block catheters when part of a polymicrobial community and confirm that thioridazine treatment remains effective at inhibiting catheter blockage under these conditions.