Bug blocker. A vaccine under development prevents adhesion proteins at the tips of spaghettilike pili on UTI-causing bacteria (left) from latching onto host cells.

Defending the Urinary Tract

Scientists have developed a genetically engineered vaccine that prevents urinary tract infections (UTIs) in mice. The findings, reported in tomorrow's issue of Science,* hold out the hope of diminishing a malady almost as common as the common cold: UTIs send 1.5 million people--mostly women--to the hospital each year in the United States alone, and 7 million more to their doctors.

The infections, caused primarily by Escherichia coli, aren't life-threatening in most cases: Standard antibiotics provide almost immediate relief. But UTIs can recur frequently, and, when untreated, cause kidney damage and even death. A vaccine could reduce this toll, but there has been "little successful work in UTI vaccines," says Harry Mobley, a microbiologist at the University of Maryland School of Medicine in Baltimore.

Until now, that is. Researchers at MedImmune, a Maryland-based biotech company, and at Washington University in St. Louis whipped up two separate vaccine formulations in the hope that at least one would successfully target an "adhesion" molecule called Filamentous H, or FimH, present on E. coli. The microbes deploy FimH on the end of long, spaghettilike strands that extend from the cell body and latch onto sugar molecules on the surface of mucosal cells. Says microbiologist Vince Fischetti of Rockefeller University in New York City, "If you block that interaction, you can prevent infection."

In one preparation, the researchers genetically engineered E. coli to express extra FimH, which they then collected and purified. In the second formulation, they modified the bacteria to express FimH and so-called chaperone proteins, which ensure that FimH folds properly. The team injected separate groups of mice with the two vaccines and exposed them 9 weeks later to UTI-causing E. coli. Both groups were able to ward off UTIs for more than 7 months. The researchers believe the vaccines triggered antibodies that bound to E. coli's natural FimH proteins, preventing the bacteria from binding to their target cells.

Experts caution that these candidate vaccines still face a long journey to the clinics. The scientists will have to demonstrate that a vaccine can block UTI-causing E. coli in humans while sparing another colony of E. coli: the beneficial intestinal flora that prevent disease-producing bugs from proliferating in the gut. Meanwhile, a different vaccine may hit the market first. A team at the University of Wisconsin, Madison, is nearing completion of midstage clinical trials of a UTI vaccine delivered via a vaginal suppository that seems to offer at least short-lived protection. Specialists are pleased with both inroads against this ubiquitous health problem. The findings, says Mobley, are "very exciting."

* For more details, Science Online subscribers can link to the full text of the Report.