Vaccine for chronic UTI could be on the horizon

A vaccine that targets a key protein used by E. coli significantly protected mice from chronic urinary tract infections (UTIs), according to a study published September 22, 2016 in Cell Host & Microbe. The results may eventually be replicated in humans, the researchers said.

Uropathogenic E. coli, the dominant cause of urinary tract infections, uses the FmlH protein to attach itself to the bladder and literally stick around for a long time. And this leads to chronic infections.

“Our findings reveal how bacteria have evolved a mechanism to colonize the bladder in order to persist and cause UTIs, and our vaccination study suggests that inhibiting this mechanism could be part of a viable approach to treating or preventing these infections,” said co-senior author Scott Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology at Washington University School of Medicine in St. Louis. MO.

Researchers had already known that E. coli uses long, hair-like pili, tipped with an adhesive protein, to attach to the bladder. But E. coli has many types of pili; it uses type 1 pili during acute infection, but until now the role of the pilus most closely related to type 1 has been unknown.

For this investigation, researchers sought to determine the function of this closely related pilus: Fml. To do so, they performed tests with infected mice.

“We found that the Fml pilus plays little to no role in acute bladder infection, but after the establishment of infection and the onset of inflammation, it contributes to the persistence of bacteria in the bladder,” said researcher Matthew Conover, PhD, who led the study as a postdoctoral researcher in Dr. Hultgren’s lab.

At the tip of the Fml pilus is the FmlH protein, which it uses to bind to the cells of the bladder wall. The researchers hypothesized that a vaccine made from FmlH would protect against chronic and recurrent infection when the bladder becomes inflamed.

To test this, the researchers vaccinated mice with one dose of the FmlH vaccine at baseline followed by a second dose 4 weeks later. They gave a mock vaccine to another group of mice using the same dosing schedule. Next, the researchers infected all the mice with E. coli and measured the amount of bacteria in their bladders and kidneys for three days.

On the first day after infection, the mice that received the vaccine showed no difference from the control mice. But by the third day, the vaccinated mice showed significantly less bacterial colonization in the bladder when compared to the vaccinated mice.

“This is a proof of concept that we can interfere with the ability of the bacteria to adhere to the bladder and reduce chronic bladder infection and spread to other parts of the body,” Dr. Hultgren said. “We are continuing to work on developing vaccines and drugs that are effective in blocking the interaction between the bacteria and the body to prevent the establishment of disease.”

In addition, the researchers showed that FmlH could bind to human bladder cell lines, which suggests that these results might be duplicated in humans. Because UTIs in humans are becoming increasingly difficult to treat due to antibiotic resistance, vaccination could be part of a strategy to prevent recurrent and chronic infections, the researchers predicted.