RESEARCHERS LEARN MORE ABOUT THE BLADDER’S RESPONSE TO INFECTION

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RESEARCHERS LEARN MORE ABOUT THE BLADDER’S RESPONSE TO INFECTION
01 August 2000 - Washington University in St Louis

Scientists studying how the bladder responds to bacteria that cause urinary tract infections are now closer to understanding why these infections keep coming back. UTIs afflict one in four American women at some point in their lives, as well as some men. Intense pain, burning and frequent urination are among the symptoms. UTIs frequently recur. A person who has had one infection is 25% more likely to have another.

To colonize the bladder, the bacteria must overcome the body’s varied and effective defenses. "It’s like an arms race," says Matthew A. Mulvey, Ph.D., the first author of the paper which appears in the Aug. 1 issue of Proceedings of the National Academy of Sciences.

Mulvey is a postdoctoral fellow in the lab of Scott H. Hultgren, Ph.D., associate professor of molecular microbiology at Washington University School of Medicine in St. Louis and senior author of the paper. Hultgren previously determined that E. coli bacteria, which cause most UTIs, attach to the bladder lining with hair-like projections called pili. The tips of the pili carry proteins that stick to the bladder lining like velcro. "The attachment keeps the bacteria from being washed away by the flow of urine, but it also alerts the bladder cells to the presence of an invader," says Joel D. Schilling, second author on the paper. These are only the opening moves of a struggle which the researchers have been able to photograph. Mulvey and John Heuser, Ph.D., professor of cell biology and physiology, along with microscopists Michael Veith and Lorraine LaRose, obtained the shots with electron microscopy of infected mouse bladders.

"What’s exciting about Matt’s work is these striking images of host-bacteria interaction," says Hultgren. "And he has gone on to elucidate the consequences of that interaction."

The photographs show the bacteria being taken into the cells of the bladder lining. This was once believed to be an effective way to destroy the bacteria, because the bladder cells would then die and slough off the bladder wall, taking the bacteria with them. "But we’ve found that the bacteria actually benefit from being taken in," explains Mulvey. Assays show that the bacteria often proliferate to high levels inside the host cells, where richer nutrients may be more readily available. When the cells die, many bacteria escape. In a movement Hultgren compares to salmon swimming upstream, they push through the layer of cells that is sloughing off to reach the inner layer.

Rather than begin to proliferate again, the bacteria may become dormant. The researchers have found, in fact, that they can lurk for weeks in the bladder lining, where they may serve as a reservoir for recurrent infections.

Physicians usually treat UTI patients with antibiotics. When bacteria and sloughed-off cells are no longer found in the urine, they conclude that the treatment has been successful. If the infection recurs, they believe that bacteria from the intestines or from outside the body have invaded the bladder again. In fact, the bladder may have been colonized all along, by dormant bacteria that were unaffected by the body’s defense systems and antibiotics.

"If these findings about the origins of recurrence are confirmed," says Mulvey, "they have the potential to change the way recurrent UTI’s are treated--not as a new disease but as a chronic one."

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