Containing a frequent, urgent—and costly—infection
Ask Harry Mobley why he’s been studying urinary tract infections (UTIs) for almost 25 years, and his answer starts with a few statistics.
“Half of all women will have a urinary tract infection some time in their life, and around 20 percent will have another one or more,” he says. Women who’ve had three UTIs are likely to continue having them, and four out of five such women get another within 18 months of the last. For reasons that aren’t fully understood, men aren’t as susceptible as women to UTIs, but prostate enlargement can up the odds, so the infections are a particular problem for older men.
Usually these infections aren’t serious, but sometimes—particularly in pregnant women—the infection reaches the kidneys, leading to more severe symptoms and increased risk of bloodstream infection. In the U.S. more than 400,000 hospitalizations a year result from UTIs that have spread to the kidneys, Mobley says.
Even the less serious infections are nothing to scoff at. Not only are they painful and annoying, but they’re also costly in terms of healthcare dollars (an estimated $3.5 billion in 2000) and lost work. “It may be only a half day, but when so many individuals are involved, the cost is significant,” says Mobley.
One principal focus of his lab has been understanding exactly how the bacterium Escherichia coli causes UTIs, and using a mouse model that closely resembles human UTIs, the group has made headway in pinning down the genes responsible for infection. In addition to this basic research, the lab in recent years has been pursuing a goal with more immediate implications for human health: developing a vaccine for UTIs caused by E. coli.
In most cases, antibiotics can quickly clear up UTIs, and if the first drug a doctor prescribes doesn’t work, another often will. “But in many women these infections are so frequent that there’s a risk for developing antibiotic-resistant bacteria because of multiple treatments with different antibiotics,” says Mobley. Antibiotics have troublesome side effects, too, including upset stomach, diarrhea and vaginal yeast infections. “So that’s where a vaccine would come in. If we can prevent these infections, women won’t have to deal with the hassle, the lost work and the risk of antibiotic resistance.”
Using genetic screening techniques on a strain of E. coli isolated from a hospitalized patient, Mobley’s lab identified six specific proteins that seemed likely candidates for conferring immunity to UTIs. They incorporated those proteins into separate vaccines and tested each one on mice that were subsequently infected with the same strain of E. coli. Then the researchers checked a week later to see how many bacteria could be found in the bladders, kidneys and spleens of vaccinated mice, compared to those of unvaccinated mice that also had been infected.
“We discovered that certain proteins protected the mice in their kidneys, and different proteins prevented E. coli from growing in the bladder,” Mobley says. “We’re currently testing combinations that we hope will protect both the bladder and the kidneys, and we have very promising data suggesting that the proteins we’ve identified can be part of a vaccine that we can eventually test in humans.”
Mobley also wanted to know whether such a vaccine would guard against infection with additional strains of E. coli. In collaboration with Gary Faerber, M.D. in the Department of Urology, Mobley and postdoctoral fellow Amanda Lloyd collected urine samples from women with frequent UTIs and used DNA hybridization techniques to learn what proteins were produced by assorted strains of E. coli during infection.
“More often than not, all of these different strains of E. coli were producing the same proteins that we were testing,” says Mobley. “So that validated our choice of proteins and suggested that if we use them in a vaccine, it will be protective against the garden variety urinary tract strains found in most patients.” And while this work involved female patients, the vaccine probably would be equally effective in men, Mobley says.
Now Mobley’s group is experimenting with ways of using only portions of the proteins, which would greatly simplify vaccine production.
“We hope,” he says, “that we are moving to a day when UTIs will be a thing of the past.” Millions of women hope so, too.
