New research has identified an interaction between a bacterial protein and fibrinogen that is found in the murine bladder following catheterization, enabling formation of a bacterial biofilm on the catheter, which is prevented by vaccination of mice with the bacterial protein.

Catheter-associated urinary tract infections (CAUTIs) are the most common cause of hospital-acquired infections. The emergence of drug-resistant bacteria has reduced available treatment options for CAUTIs, and new therapeutic strategies are urgently required.

Enterococci account for 15% of CAUTIs, and the pathogenesis of Enterococcus faecalis UTI derives from its ability to form biofilms on catheters-E. faecalis is highly attenuated in the absence of catheterization in a murine model. A bacterial pilus consisting of three protein subunits contributes to biofilm formation; the EbpA subunit, which forms the tip of the pilus, is known to be involved in CAUTI.

The N-terminal domain of EbpA contains a MIDAS motif, which is typically involved in cellular adherence. Deletion or mutation of the EbpA MIDAS motif diminished in vitro biofilm formation. Sequence analysis of the EbpA N-terminus suggested the presence of a fibrinogen-binding domain. In vitro, fibrinogen binding was observed with wild-type EbpA, but not with the mutant isoforms.

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In a murine model of urinary bladder catheterization, fibrinogen was found to be released into the bladder as early as 1 h after catheter implantation. When catheterized mice were challenged with wild-type E. faecalis, the bacteria colocalized with fibrinogen on the catheter and on bladder urothelium, whereas E. faecalis lacking wild-type EbpA were not detected on either surface.

The requirement for fibrinogen in E. faecalis biofilm formation was further demonstrated by the observation of poor bacterial growth in human urine in vitro. Supplementation of the urine with fibrinogen stimulated biofilm formation by wild-type bacteria, but not by bacteria with EbpA MIDAS-motif mutations. Furthermore, vaccination of mice with either full-length EbpA protein or the EbpA N-terminal domain produced a long-lasting immune response that protected the animals against CAUTI induced by E. faecalis. Sera from vaccinated mice blocked the interaction between EbpA and fibrinogen in vitro.

Vaccinations targeting bacterial biofilm formation could provide a new therapeutic approach for prevention of CAUTIs. Whether this model is transferable to humans and to other CAUTI pathogens must now be tested.