Bacteria in Urinary Tract Infections Invade Bladder Cells

Scientists at Washington University School of Medicine in St. Louis have found definitive proof that some of the bacteria that plague women with urinary tract infections (UTIs) are entrenched inside human bladder cells.

The finding confirms a controversial revision of scientists' model of how bacteria cause UTIs. Previously, most researchers assumed that the bacteria responsible for infections get into the bladder but do not invade the individual cells that line the interior of the bladder.

"Our animal model of UTIs has allowed us to make a number of predictions about human UTIs, but at the end of the day, we felt it was critical to show this in humans, and now we've done just that," says senior author Scott J. Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology at the School of Medicine.

The results appear in the December issue of Public Library of Science Medicine.

Fully understanding what bacteria do in the bladder is critical to developing better diagnoses and treatments for UTIs, Hultgren says. The bacterium Escherchia coli is thought to be responsible for 80 percent to 90 percent of UTIs, which occur mainly in women and are one of the most common bacterial infections in the United States. Scientists estimate that more than half of all women will experience a UTI in their lifetimes, and recurrent UTIs will affect 20 percent to 40 percent of those patients.

"Recurrence is one of the biggest problems of UTIs," says Hultgren. "Even though we have treatments that eliminate the acute symptoms, the fact that the disease keeps recurring in so many women tells me that we need to develop better treatments."

Prior to the work of Hultgren and his colleagues, most microbiologists and urologists believed for a variety of reasons that E. coli wasn't getting into bladder cells.

"For example, there is a barrier in the bladder that prevents toxins and other things in your urine from leaking back into the body," notes David Rosen, an M.D./Ph.D. student at the School of Medicine and lead author of the paper. "And it was thought that bacteria could not penetrate that barrier."

A biopsy could reveal the presence of bacteria in bladder cells, but taking a tissue sample in an infected bladder incurs an unacceptable risk of allowing bacteria to spread into the bloodstream, a dangerous condition called sepsis.

Scientists also thought that if the bacteria were getting into bladder cells, they would replicate and spread rapidly, sometimes leading to sepsis. But after Hultgren first discovered that bacteria are able to invade bladder cells in 1998, he later found evidence in his animal model that bacteria could establish residence inside those cells. He showed that this process involved several behavioral changes that allow the bacteria to form cooperative communities known as biofilms. By working together, bacteria in biofilms build themselves into structures that are more firmly anchored in infected cells and are more resistant to immune system assaults and antibiotic treatments.