Researchers identify protein critical in causing chronic urinary tract infections

September 22, 2016, Washington University in St. Louis
Researchers have identified a way to prevent chronic urinary tract infections, a common infection primarily caused by E. coli (shown above). Vaccinating mice against a key protein that E. coli use to latch onto the bladder and cause UTIs reduces severe disease, according to researchers at Washington University School of Medicine in St. Louis. Credit: Scott Hultgren, John Heuser

Researchers have identified a potential way to prevent chronic urinary tract infections (UTIs). Their research points to a key protein that bacteria use to latch onto the bladder and cause UTIs, according to scientists at Washington University School of Medicine in St. Louis. Vaccinating mice against the protein reduces the ability of bacteria to cause severe disease.

The study, published Sept. 22 in Cell Host & Microbe, suggests that targeting this protein may prevent the most serious consequences of a very common infection.

"Our findings reveal how bacteria have evolved a mechanism to colonize the 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 Scott Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology and one of the study's senior authors.

UTIs are one of the most common infections, accounting for 8.1 million visits to health-care providers in the United States every year. Women stand about a one-in-two chance of contracting one over their lifetimes. About 80 percent of UTIs are caused by Escherichia coli (E. coli).

Acute UTIs are characterized by frequent painful urination and abdominal or back pain and typically are treated with antibiotics, although multidrug resistance is a growing problem. Untreated – or untreatable – chronic infections allow a pool of bacteria to survive in the bladder and possibly spread to the kidneys or the bloodstream, where they can cause disease severe enough to require hospitalization.

To avoid being swept away during urination, E. coli attaches to the bladder with long, hairlike projections called pili. One kind of pilus, called type 1, is necessary in the early stages of infection. Another research team identified a second pilus, called Fml, with genes that are strikingly similar to the type 1 pilus but whose function had been unknown.

As part of the current study, Hultgren, postdoctoral researcher Matthew Conover, PhD, colleagues Ségolène Ruer, PhD, and Han Remaut, PhD, of Vrije Universiteit Brussel in Belgium, and others set out to determine the function of the Fml pilus. They focused on a protein known as FmlH, which they believed was located at the tip of the pilus, where it would help bacteria stick to the bladder wall.

The researchers removed the gene for FmlH from E. coli and then infected the urinary tracts of with bacteria with and without the gene. They found that E. coli lacking FmlH were less likely to establish chronic infections in mice than bacteria with the protein.

In the first few days of the infection, the two strains multiplied to similar levels. But by the end of the fourth week, the bacteria without FmlH were 1,000 times less numerous in the bladder and 100 times less numerous in the kidneys than the bacteria with the protein.

"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 Conover, who led the study as a researcher in Hultgren's lab but now works for iCubate, a biomedical company.

Further, the researchers showed that FmlH could bind to human bladder cell lines, indicating that the results they saw in mice may be applicable to humans.

"Taking biopsies of human bladders during a UTI would be contraindicated because of the risk of spreading the bacteria, so the cell lines are the best model of human infection we have," Conover said.

UTIs are becoming increasingly difficult to treat as multidrug resistance becomes more common. Vaccination could be part of a strategy to prevent recurrent and chronic infections.

The researchers gave a group of mice two doses of vaccine made from a piece of the FmlH protein, four weeks apart, and another group of mice mock vaccinations without the protein. Then, they infected both groups with E. coli and measured the amount of bacteria in their bladders and kidneys one, two and three days after infection. On the first day, there was no difference between the mice that received the vaccine and those that didn't. But by the third day, the unvaccinated mice had more than 1,000 times more bacteria in their bladders and 100 times more bacteria in their kidneys than 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," Hultgren said. "We are continuing to work on developing vaccines and drugs that are effective in blocking the interaction between the and the body to prevent the establishment of disease."

Explore further: Human urine helps prevent bacteria from sticking to bladder cells

Related Stories

Human urine helps prevent bacteria from sticking to bladder cells

June 30, 2015
Human urine contains factors that prevent a common culprit in urinary tract infections (UTIs), uropathogenic Escherichia coli bacteria, from properly attaching to bladder cells, a necessary step for infection. The research, ...

Although uncommon, kids can get UTIs, too

May 25, 2016
Dear Mayo Clinic: My daughter is 3 and has had two urinary tract infections in the last six months. Is this common in kids? What can we do to prevent a future infection, and does this mean she will always be more susceptible?

Newly described cellular defense activity could guide solutions to UTIs

July 19, 2016
The process cells use to secrete chemicals also appears to be the way to clear urinary tract infections, or UTIs, according to a study by researchers from Duke Health and Duke-National University of Singapore Medical School.

How UTIs in women may damage kidneys

November 8, 2013
A scientist from the Institute of Translational Medicine has been awarded a £190,000 Fellowship by Kidney Research UK to investigate how the E.coli bacteria which cause Urinary Tract Infections (UTIs) move to the kidneys ...

Towards better treatment of cystitis

August 30, 2016
Every year, millions of people are treated for cystitis, but despite its prevalence, the disease is still a scientific mystery. Now a research team from University of Southern Denmark has succeeded in identifying how the ...

Bladder cells regurgitate bacteria to prevent urinary tract infections

May 28, 2015
Duke Medicine researchers have found that bladder cells have a highly effective way to combat E. coli bacteria that cause urinary tract infections (UTIs).

Recommended for you

Scientists grow human esophagus in lab

September 20, 2018
Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.

Study identifies stem cell that gives rise to new bone and cartilage in humans

September 20, 2018
A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

Researchers identify human skeletal stem cells

September 20, 2018
Human skeletal stem cells that become bone, cartilage, or stroma cells have been isolated from fetal and adult bones. This is the first time that skeletal stem cells, which had been observed in rodent models, have been identified ...

A new app enables a smartphone to ID bacteria in just one hour

September 20, 2018
In a potential game changer for the health care industry, a new cell phone app and lab kit now allow a smartphone to identify bacteria from patients anywhere in the world. With the new app, doctors will be able to diagnose ...

Synthetic sandalwood found to prolong human hair growth

September 19, 2018
A team of researchers led by Ralf Paus of the University of Manchester has found that applying sandalwood to the scalp can prolong human hair growth. In their paper published in the journal Nature Communications, the group ...

Zombie cells found in brains of mice prior to cognitive loss

September 19, 2018
Zombie cells are the ones that can't die but are equally unable to perform the functions of a normal cell. These zombie, or senescent, cells are implicated in a number of age-related diseases. And with a new letter in Nature, ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.