Biofilms may be responsible for recurring bladder infections

Bacteria that invade bladder cells and grow into structured colonies known as biofilms may be responsible for many recurrent urinary tract infections (UTIs), according to School of Medicine researchers.

The findings, based on animal studies, offer a new explanation for recurrent UTIs and why the body’s defenses or antibiotic treatments often don’t cure the infections. The study is the first to report disease-causing biofilms inside of cells and may provide new insight into other recurring infections such as ear infections, or otitis media.

The findings and a commentary about their implications were published in a recent issue of Science.

For decades, doctors have believed that UTIs are acute infections caused by bacteria that are introduced repeatedly into the urinary tract. Sexual intercourse is associated with UTIs, as is poor hygiene.

“But it’s very frustrating for women who know they are practicing good hygiene but still have these recurrent infections,” said principal investigator Scott J. Hultgren, Ph.D., the Helen Lehbrink Stoever Professor of Molecular Microbiology. “Our work may explain why urinary tract infections are such a problem. We show that the bladder itself may be a reservoir for bacteria that are protected and emerge periodically to cause recurrent infection.”

UTIs are the second most common bacterial infection in humans after respiratory infections. They are thought to account for 100,000 hospital admissions, 8 million physician office visits and $1.6 billion in medical expenditures annually in the United States.

They affect mainly women, 50 percent of whom are thought to experience at least one UTI during their lives. Of these, 20 percent to 40 percent will develop one or more recurrent infections. The bacterium Escherichia coli (E. coli) accounts for about 80 percent of all UTIs.

The investigators inoculated the bladders of normal and immune-deficient mice using E. coli known to cause UTIs in humans. They found that the bacteria first pass beneath a protective layer consisting of a substance known as uroplakin, which coats the surface of cells lining the bladder.

Upon invading the cells, the bacteria multiply and form a loose colony of rod-shaped microbes. The colony grows until it forms a pod that bulges from the cell’s surface and is covered by an impermeable layer of uroplakin.

As the pod develops, the thousands of bacteria within take on a smaller, rounded shape. They also produce a meshwork of fibers that anchors them to the surrounding matrix and to each other. This kind of organization is the hallmark of biofilms formed by bacteria in the lungs during cystic fibrosis and of biofilms in bodies of water around the world.

“The bacteria rest in the matrix like eggs in an egg carton,” said Joseph J. Palermo, M.D., Ph.D., a fellow working in Hultgren’s laboratory and a co-author of the report.

The covering of uroplakin protects the biofilm like an eggshell and shields the bacteria from immune-system defenses and antibiotic therapy.

“The bacteria then begin detaching from the biofilm and leave the cell to re-initiate an acute infection in the urinary tract,” said lead author Gregory G. Anderson, a graduate student in Hultgren’s laboratory.

Hultgren’s colleagues are now designing new therapies that will attack the biofilm as well as studying how the host responds to the infection.

Hultgren, in collaboration with other researchers at the University and at the University of Washington, is also researching the genetic and molecular basis by which E. coli cause UTIs and is initiating studies that should determine whether UTIs in humans also involve formation of pod-like biofilms.