Unlocking the Mechanics of the Urinary Tract Infection

New research helps explain how bacteria send their victims running to the bathroom.

Lucy Nicholson / Reuters

Anyone who’s ever had a urinary tract infection knows how awful it can be: running to the bathroom every 10 minutes, only to experience painful, burning urination once you get there. According to the National Institutes of Health, UTIs are the second most common type of infection, accounting for more than 8 million trips to the doctor each year. They’re especially common in women—the odds that a woman will experience a UTI at some point in her lifetime are higher than 50 percent—and each new infection increases the likelihood of a recurrent problem.

UTIs became so ubiquitous that in recent years, some physicians have argued in favor of making the antibiotics that cure them available over the counter.  “There was a big discussion in the U.K. about releasing antibiotics without prescription,” says Timm Maier, a professor of biology at the University of Basel, Switzerland, “To make it easier and to reduce the cost of going to the doctor” for patients who already are familiar with the symptoms and can diagnose themselves.

Around 80 percent of UTIs are caused by Escherichia coli, a bacterium often found in the human gut. Most of the time, E. coli bacteria are harmless—but some strains are extraintestinal pathogens, escaping the gut and climbing up the urinary tract to cause infection. And as recent study published in the journal Nature demonstrated, those particular pathogens are experts at clinging to our insides.

An E. coli bacterium looks a bit like a squid, with a bunch of long filaments protruding from the body. At the end of each of those filaments is a specific protein called FimH, which can change its shape to form a tiny hook; with that hook, the bacterium hangs on to a particular sugar molecule on the outside of human cells, called a ligand. “It’s not the type of sugar we put in our coffee, but it’s a close relative,” says Maier, one of the study’s co-authors. The filaments, “are really long and they only grab at the very ends,” he explains, likening the hooking mechanism to the tip of arrow—once you push it through a surface, you can’t pull it back out. That enables E. coli to stay attached to human cells even when we pee, which generates rather strong currents, at least by bacterial standards. In fact, the stronger E. coli is pulled by those currents, the tighter it holds on to the ligand molecule.

But once the “urinary storm” is over, FimH can change its shape again and pull out its hook, letting the bacteria move up the urinary tract.  Maier and one of his study co-authors, Beat Ernst, a molecular-pharmacy researcher at the University of Basel, observed this behavior in a petri dish coated with ligand molecules.  “They release the lock and the ligands, and are free to swim with their little motors,” Maier says—the bacterium comes equipped with thrusters that propel it up the urinary tract like a tiny submarine.

Interestingly, all that clinging and swimming activity goes pretty much undetected by the human body. The tiny hooks digging into our cells don’t cause the characteristic sensations of a UTI; rather, the pain and burning come from the later stage of infection at which E. coli forms a biofilm, a thriving bacterial community.  At that advanced stage, E. coli breaks our cells, causing pain and sometimes bleeding, and eats the cellular debris it creates. “They feed on floating extracellular material, all kinds of components,” Maier says. “They’re very versatile in metabolizing compounds.”

Scientists don’t yet have a full grasp of how we acquire E. coli, in part because these infections are hard to trace—the bacterium may sneak in through the digestive system and lie dormant for weeks or months. And not all infections get an epidemiological record—if a case is obviously a UTI, doctors may phone in prescriptions without running tests, says Amee Manges, a researcher at the University of British Columbia who studied how humans acquire E. coli. Infections likely come from multiple sources. Some may be passed from person to person, and others through food.  In young women, transmission of E. coli has been linked to frequent or recent intercourse; in older women, to hospital stays. UTIs may also be caused by food-borne bacteria: In a recent study, Manges found genetic similarities between the E. coli strains present in humans and in chicken meat. These strains may be particularly antibiotic-resistant, because of the antibiotics used in chicken feed.

But as E. coli gets better at beating antibiotics, making them available over the counter will become a useless fix. Antibiotics work by breaking bacterial cells or affecting their metabolism. “But they basically act on most of the bacteria with little specificity—and they tend to increase resistance in the overall bacterial population,” Maier says.  That’s why he and Ernst are looking at alternative mechanisms of defeating E. coli—such as preventing it from attaching to human cells in the first place. Now that they and their colleagues have identified the behavior of the protein FimH, they can start devising mechanisms that prevent that attachment.  If they find a way to block the little hooks on the E. coli’s filaments, they may be one step closer to an alternative treatment for UTIs.  “The advantage of anti-adhesive therapy over antibiotics,” Ernst says, “is that it has a much lower chance for resistance.”