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Sticky problem. E. coli bacteria attach to host cells using adhesive-tipped hairs.

Disentangling a Hairy Infection

It's not a pleasant thought, but the bacteria that cause urinary tract infections use tough, hairlike fibers tipped with adhesive to latch onto the lining of our kidneys and bladder. In the United States alone, the pesky bugs send 8 million people to the doctor each year. But new treatments for these painful infections and other diseases could be on the horizon, now that researchers have figured out how bacteria create those sticky fibers.

Many kinds of bacteria create so-called pili fibers, including the Escherichia coli responsible for urinary tract infections and the Yersinia pestis bacteria that cause bubonic plague. Pili fibers are towers of interlocking blocks of cells, stacked so that a dangling tail on each block fits neatly into a groove in the block below it. Researchers know that two common types of proteins--dubbed chaperones and ushers--somehow control pili assembly. Chaperones help other proteins fold into the right shapes and protect them from interactions that might cause trouble. Ushers, as their name suggests, ensure that chaperones bring proteins to the right location. But how these proteins actually assemble a pilus fiber wasn't known.

Taking up the challenge, microbiologist Scott Hultgren and molecular biophysicist Gabriel Waksman and colleagues at Washington University in St. Louis, Missouri, painstakingly took series of x-ray photographs of pilus fibers under construction. Studying the assembly process frame by frame, the team found that once the individual blocks, or subunits, are created inside the bacteria, a chaperone protein loosely fills in the empty groove on the subunit. The chaperone prevents the subunit from interacting with other proteins and carts it off to an usher protein on the bacterium's outer membrane. There, the chaperone detaches, and the subunit latches onto the dangling tail of another subunit. Thus connected, the subunits push up through the cell membrane to form a strong, stable fiber, the team reports in the 15 November issue of Cell.

The study could lead to new strategies to treat urinary tract infections, says structural biologist Katrina Forest of the University of Wisconsin, Madison. Now that it's clear how pili are made, researchers can focus on halting subunit assembly or taking the pilus apart, she adds. The research might also lead to new insight into how chaperone proteins aid in the development of other complex molecular structures, says microbiologist David Thanassi of the State University of New York, Stony Brook, calling the research “remarkable and significant.”

Related sites
Scott Hultgren's site
Gabriel Waksman's site
David Thanassi's site
Katrina Forest's site