Researchers Develop Vaccine To Prevent Catheter-Associated UTIs

By C. Rajan, contributing writer

Researchers at Washington University School of Medicine in St. Louis have developed an experimental vaccine which may prevent the most common type of infections patients pick up in hospitals. In their study in mice models, this vaccine effectively prevented urinary tract infections that are caused by catheters. 

Catheters are routinely used in hospitals to drain urine from a patient’s bladder, and they carry a considerable risk of urinary tract infections. Patient with catheters inserted for more than 30 days almost certainly acquire a urinary tract infection. Urinary tract infections are a painful condition, which, if left untreated, can lead to bladder damage and even cause life-threatening sepsis.

“Catheter-associated urinary tract infections are very common,” said Dr. Ana Lidia Flores-Mireles, lead author and a postdoctoral research associate in the laboratory of Dr. Scott Hultgren. “Antibiotic resistance is increasing rapidly in the bacteria that cause these infections, so developing new treatments is a priority.”

Catheters used in hospitals are typically coated with antibiotics to reduce the risk of infection. However, inserting catheters into the bladder causes an inflammatory response that results in the catheter being covered with a blood-clotting protein known as fibrinogen. The researchers found that the bacteria used long, thin hairs known as pili to anchor themselves to the fibrinogen and form biofilms which protected the bacteria from antibiotics and immune cells and enabled bacteria to infect the lining of the bladder.

In the study, Flores-Mireles and her colleagues used the bacteria Enterococcus faecalis, which is a common cause of catheter-associated urinary tract infections. They found that a protein on the end of the pili, EbpA, was actually responsible for binding to fibrinogen and allowing the bacteria to begin forming biofilms. 

Working on mice models, the researchers surgically implanted a small segment of catheter into the bladder and exposed the mice to E. faecalis. When they prevented these bacteria from making EbpA, they couldn’t start infections in the mice.

The researchers then injected the mice with a vaccine containing EbpA which caused an immune system response of antibody production, resulting in blocking of the EbpA and stopping the infectious process.

As the next steps, the researchers are testing whether the vaccine can help mice fight and conquer established infections of E. faecalis. They are also trying to develop a monoclonal antibody that can block the EbpA protein, thus preventing catheter-associated infections.

“We took a closer look at this protein and found that one-half of it is essential for binding to fibrinogen to induce infections,” Flores-Mireles said. “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.”

The study is available online Sept. 17 in Science Translational Medicine.