Scientists image key steps in bacterial...( St. Louis Aug. 12 1999 -- F...)

St. Louis, Aug. 12, 1999 -- For the first time, scientists have obtained 3-D snapshots of crucial steps in bacterial infection. One set of X-ray images should aid in the fight against bladder infection. A second set captures a key event in kidney infection. The two papers appear in the Aug. 13 issue of Science.

"These are the first detailed snapshots of the basis for an interaction between a disease-causing bacterium and its host," says Scott J. Hultgren, Ph.D., professor of molecular microbiology at Washington University School of Medicine in St. Louis. Hultgren heads the research program that spawned the two imaging studies, and he is a co-author of the two papers.

Over the past 10 years, Hultgren's group has determined how E. coli makes sticky hairs called pili, which many other types of bacteria produce as well. These hairs enable bacteria to cling to tissue instead of getting swept away by bodily fluids such as urine. When bald, the bacteria cannot cause infections. So preventing pili from being made or doing their job should be an effective, new antimicrobial strategy.

Hultgren's team has identified the major players in pilus assembly. These include:

• protein subunits that eventually are assembled into pili,
• boomerang-shaped proteins called chaperones that ferry the subunits to the bacterial cell surface,
• doughnut-shaped proteins called ushers that assemble and extrude pili.

The first pilus subunits to emerge through the usher are different from the rest. These adhesins give the pilus the sticky tip that enables the bacterium to get a toehold in human tissue. Hultgren and colleagues previously showed that E. coli lacking adhesin is unable to infect the bladder. And in collaboration with MedImmune Inc., they demonstrated in a mouse model that the adhesin is an effective vaccine -- it primes the immune system to disarm any E. coli that carry the same protein. Hultgren also has been collaborating with a drug
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Contact: Linda Sage
sage@medicine.wustl.edu
314-286-0119
Washington University School of Medicine
13-Aug-1999