Durable fluid-like surface for sustainable biofilm inhibition

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Catheter-associated urinary tract infections (CAUTIs) account for more than 30% of acute care hospital infections. Bacterial pathogens initially colonize and form biofilm on the catheters, and invade the bladder and eventually the upper urinary tracts. Prolonged catheterization (~30 days) can increase the chance of CAUTIs to 100%. Antibiotics prescribed for symptomatic CAUTIs are frequently unable to kill bacteria within the biofilm. Therefore, inhibiting biofilm formation will significantly reduce the chance of CAUTIs. Catheter biofilms are often polymicrobial with mixed bacterial communities. Durable biosurface coatings would be an advantageous approach to inhibit biofilm formation without external control. Existing anti-bacterial surfaces include bactericidal surfaces (e.g., antimicrobial peptide or silver modified surfaces) and anti-biofouling surfaces (e.g., hydrogel or poly(ethyleneglycol) based polymer coatings), but all existing approaches are unable to inhibit biofilm formation on catheters for a prolonged period. Here, we propose a conceptually new fluid-like and non-sticky biosurface, namely a quasi-liquid surface, which can potentially inhibit biofilm for over 30 days. The quasi-liquid surface will be made by tethering flexible polymer onto catheter materials with chemical bonding. The untethered end is highly mobile and behave like a fluid. The innovation is to change the solid/bacterial interaction to quasi- liquid/bacterial interaction and inhibit polymicrobial biofilm without directly killing bacteria. Our central hypothesis is that the fluid-like surface will prevent protein adsorption and inhibit polymicrobial biofilm as an integrated community during long-term catheterization. We will validate the hypothesis with two aims: (1) to study the mechanism of E. coli biofilm inhibition, and (2) to validate biofilm inhibition of clinical isolates (i.e., uropathogenic strains) on the quasi-liquid surface. The team includes PI Dai at UT Dallas with expertise in biosurfaces and microfluidics, Co-I Palmer with expertise in microbiology and antibiotic resistance in pathogenic bacteria, and our collaborator Zimmern at UT Southwestern Medical Center with expertise in the management of complicated UTIs in a variety of clinical settings. This two-year project aims to inhibit polymicrobial biofilm over 30 days that is challenging by a microbiological approach alone. The development of this novel quasi-liquid surface and the understanding of the quasi-liquid/bacterial interaction will not only benefit the management of CAUTIs but also open new avenues to better combat biofilms forming on other human implant devices.