Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections

Area of Science:

• Microbiology
• Biomaterials Science
• Infectious Diseases

Background:

• Microbial adhesion to medical devices, especially urinary catheters, is a primary cause of hospital-acquired infections and contributes to antimicrobial resistance.
• Host serum proteins, like fibrinogen (Fg), deposit on urinary catheters due to bladder inflammation, serving as a scaffold for pathogens such as *Enterococcus faecalis*.
• This pathogen-host protein interaction promotes persistent bladder colonization and complicates antibiotic treatments.

Purpose of the Study:

• To investigate the role of deposited host proteins, specifically fibrinogen, as a scaffold for uropathogen adhesion and colonization on urinary catheters.
• To evaluate the efficacy of liquid-infused silicone catheters in reducing host protein deposition and subsequent microbial colonization in a mouse model of catheter-associated urinary tract infections (CAUTIs).

Main Methods:

• Utilized a mouse model of CAUTI to assess the impact of liquid-infused silicone catheters on host protein deposition and microbial colonization.
• Employed proteomics to analyze the composition of host-secreted proteins deposited on conventional versus liquid-infused catheter surfaces.
• Quantified microbial colonization on catheters, in bladders, and systemic dissemination in vivo.

Main Results:

• Deposited fibrinogen was found to be advantageous for the adhesion and persistence of multiple uropathogens, including *E. faecalis*, *E. coli*, *P. aeruginosa*, *K. pneumoniae*, *A. baumannii*, and *C. albicans*.
• Liquid-infused silicone catheters significantly reduced host protein deposition compared to conventional catheters.
• This reduction in protein deposition correlated with decreased microbial colonization on catheters, in bladders, and reduced systemic dissemination in the CAUTI mouse model.

Conclusions:

• Targeting the deposition of microbial-binding scaffolds, such as fibrinogen, on medical devices presents a promising antibiotic-sparing strategy for preventing and treating CAUTIs.
• Liquid-infused catheters demonstrate potential as an effective intervention to mitigate catheter-associated infections by reducing pathogen adherence.
• The findings suggest a broader applicability of this approach to other medical device-related infections characterized by biofilm formation and host protein interactions.