Blocking Binding of Bacteria to Fibrinogen Prevents Biofilm Formation and Catheter-Associated Bladder Infection in Mice

A team of molecular microbiologists has identified and targeted a critical step in biofilm formation and developed a vaccine that prevents catheter-associated urinary tract infections in mice.

Enterococci bacteria are a frequent cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infection. Treatment has become increasingly difficult due to the emergence of multiantibiotic-resistant enterococcal strains and their ability to form biofilms on catheters. Furthermore, the insertion of a catheter into the bladder provokes an inflammatory response that results in the catheter being covered with the blood-clotting protein fibrinogen, which shields bacteria from the antibiotics.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a mouse model that demonstrated formation of catheter-associated biofilms by Enterococcus faecalis.

They reported in the September 17, 2014, online edition of the journal Science Translational Medicine that biofilm formation depended on EbpA, which is the minor subunit at the tip of a heteropolymeric surface fiber known as the endocarditis- and biofilm-associated pilus (Ebp).

EbpA is a protein of the adhesin family that mediates bacterial attachment to host fibrinogen, which is released and deposited on catheters after introduction of the catheter into the mouse bladder. Fibrinogen-binding activity resides in the amino-terminal domain of EbpA (EbpANTD), and vaccination with EbpA and EbpANTD, but not its carboxyl-terminal domain or other Ebp subunits, inhibited biofilm formation in vivo and protected against catheter-associated urinary tract infection.

Analyses in vitro demonstrated that anti-bacterial protection was associated with a serum antibody response that blocked EbpA binding to fibrinogen and the formation of a fibrinogen-dependent biofilm on catheters.

“Catheter-associated urinary tract infections are very common,” said first author, Dr. Ana Lidia Flores-Mireles, a postdoctoral research associate in molecular microbiology at the Washington University School of Medicine. “Antibiotic resistance is increasing rapidly in the bacteria that cause these infections, so developing new treatments is a priority.”

“We took a closer look at this protein and found that one-half of it is essential for binding to fibrinogen to induce infections,” said Dr. Flores-Mireles. “This protein is like the anchor of a boat. Without the anchor, the infection is at the mercy of the waves and gets washed away. The segment of genetic code that makes this part of the protein is also found in the genes of many other bacteria that cause urinary tract infections, so a vaccine, antibody, or drug that blocks this part of the protein may help prevent other infections linked to catheters in the urinary tract and in other parts of the body.”

Related Links:
Washington University School of Medicine