Hultgren Receives Prestigious Eli Lilly Award

"Our strategy is to decipher the molecular basis of how bacteria cause disease and to use this information to design vaccines and novel antibacterial therapeutics," Hultgren says. "There is an urgent need for such products now that bacterial infections are becoming increasingly more difficult to treat due to the rising tide of antibiotic-resistant microbes."

Like many other bacteria, E. coli attaches to host tissue with sticky hairs. The hairs, or pili, are sticky because their feathery tips contain a protein called an adhesin, which fits into receptors in the urinary tract like keys into locks. Anchored in place, the bacterium can multiply rather than being washed away by the stream of urine.

Combining genetic manipulations with cell biology, protein chemistry, high-resolution electron microscopy and x-ray crystallography, Hultgren and colleagues are following three lines of research. First, they are determining the 3-D structure of the adhesin, hoping to find out how the protein's shape enables it to interact with host receptors. Second, they are investigating the consequences of this interaction and the cross-talk that switches on genes in both pathogen and host.

In the third program, Hultgren's team is studying the structure, function and assembly of E. coli P and type 1 pili, whose tips contain adhesins called PapG (on P pili) and FimH (on type 1 pili). For many years, researchers have been trying to purify these proteins for use as vaccines against urinary tract infections, but without success. Hultgren and colleagues have succeeded because they uncovered and made use of key facts about pilusassembly.

During nine years of painstaking research, the group discovered that a protein called a chaperone plays a critical role in molding pilus subunits and adhesins into their correct 3-D shapes and transporting them to the membrane that surrounds the bacterial cell. Another protein, called an usher, extrudes a

Contact: Linda Sage
Washington University School of Medicine

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