Researchers Find Out How The Bladder Responds To Infection

November 19, 1998

St. Louis, Nov. 19, 1998 -- Scientists have discovered how the bladder responds to bacteria that cause cystitis. They also have found that the bacteria can hide out within the bladder lining, where they could promote further bouts of infection.

"We discovered that cells that line the bladder have a built-in defense mechanism that kicks in when bacteria attach to them - they commit suicide and slough off," says Scott J. Hultgren, Ph.D., who directed the research. "But we also found that some of the bacteria avoid being removed from the bladder by invading underlying cells."

Hultgren is an associate professor of molecular microbiology at Washington University School of Medicine in St. Louis. One of his postdoctoral fellows, Matthew A. Mulvey, Ph.D., is first author of the paper, which appears in the Nov. 20 issue of Science.

Cystitis, or bladder infection, sends 7 million women to the doctor each year. Intense pain, burning and frequent urination are among its symptoms.

Hultgren's group previously determined that cystitis-causing E. coli attach to the bladder lining with hair-like projections called type I pili. The pili are tipped with a protein that locks into receptors on the bladder lining like velcro, enabling the bacteria to cling.

Mulvey wanted to know how the bladder responds to bacterial infection, so he enlisted the help of electron microscopists John Heuser, Ph.D., professor of cell biology and physiology, and G. Michael Veith, senior microscopist in biology.

Images of mouse bladders two hours after infection showed E. coli adhering to the lining. These are the first high-resolution snapshots revealing how bacteria can cling to cells.

Covering the bladder lining were hexagonal tiles of proteins called uroplakins. The pili were interacting directly with the uroplakin layer, and they were much shorter than when E. coli grows in broth. "Either pilus retraction or hindrance of pilus growth could result in the pile up of unassembled pilus components in the bacteria, and this is known to switch on certain genes," Hultgren says. "So this could be how E. coli senses that it has attached to the bladder lining."

After the bacteria adhered, many of the cells lining the bladder sloughed off, carrying the attached bacteria with them. Six hours after infection, about 90 percent of the bacteria were lost, and underlying bladder cells were exposed. "This process of bladder cell elimination is thought to be a natural defense mechanism of the urinary tract," Hultgren says.

It also may be an example of altruistic suicide by animal cells in response to infection. Mulvey showed that the bladder cells activated protein-destroying enzymes and cut up their DNA before they sloughed off. "It's fantastic first line of defense to have a group of cells purposefully killing themselves in order to protect the rest of the tissue," he says.

Twelve hours after infection, mouse bladders treated with a cell suicide-preventing drug contained 85 percent more bacteria than untreated bladders. "This supports the idea that suicide of infected bladder cells helps clear the bacteria," Mulvey says.

The researchers were surprised to find that a laboratory strain of E. coli with type I pili was as effective at provoking the suicide response as the clinical strain of E. coli. But the same two strains lacking FimH - the adhesive protein at the tips of type I pili - were ignored by bladder cells. "These experiments show that bacterial attachment by FimH is a critical step in triggering the suicide response of bladder cells," Mulvey says.

Despite the bladder's vigorous response to E. coli, significant numbers of bacteria remained 48 hours after infection. Most weren't on the surface, however. Electron micrographs taken two hours after infection showed the bacteria invading the bladder lining, which seemed to be enveloping them. Using biochemical techniques, Mulvey determined that most of the bacteria persisting within the bladder after two days appeared to be hiding out within bladder cells.

"This suggests that the bacteria can resist the bladder's built-in defense mechanism by invading into deeper tissue," Hultgren says. "That may explain why many patients have recurrent bladder infections despite antibiotic treatment, which may not efficiently kill bacteria protected within the bladder cells."

Hultgren's work eventually may help women avoid bladder infections altogether. His group has developed FimH into a vaccine that proved effective against cystitis in mice and should be tested in humans within the next two years. "A vaccine could prevent all of this from occurring in the first place," Hultgren says.
Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ. Induction and evasion of host defenses by type I-piliated uropathogenic Escherichia coli. Science, Nov. 13, 1998.

A grant and fellowship from the National Institutes of Health and a Lucille P. Markey Special Emphasis Pathway in Human Pathobiology fellowship supported this research.

Washington University School of Medicine

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to