October 7, 1999-- Researchers from the Howard Hughes Medical Institute (HHMI) have determined the three-dimensional structure of invasin, a protein that allows a close relative of the bubonic plague bacteria to infect intestinal cells and cause food poisoning.

When the bacterium Yersinia pseudotuberculosis is consumed in contaminated food, it gains access to certain cells in the intestinal epithelium called M cells. Once inside the intestines, Y. pseudotuberculosis, which is related to the organism that causes bubonic plague, binds to receptors on M cells. This leads to the entry of the bacteria into regional lymph nodes in the intestine. The growth of bacterial colonies in the lymph nodes triggers intense nausea, vomiting and diarrhea. It turns out that invasin is crucial to the bacterium's ability to establish a foothold in the lymph nodes, says Ralph Isberg, an HHMI investigator at Tufts University School of Medicine.

When Isberg first began studying Y. pseudotuberculosis in the 1980s, "there was very little known about how any bacterium was able to enter into an animal cell and trigger infection," he said.

To better understand how Y. pseudotuberculosis causes illness, Isberg set about cloning genes from Y. pseudotuberculosis and inserting them one by one into a second bacterium used frequently in laboratory research. He realized he had made an important discovery when a strain of the laboratory bacterium harboring a single Y. pseudotuberculosis gene had acquired the ability to enter animal cells. "This single gene (inv), and the invasin protein it coded for, was sufficient for infection of cells in culture," Isberg said.

Researchers now know that the aptly named bacterial protein binds more tightly to integrins -- the receptors for invasin -- than do other proteins, or ligands. To learn how invasin out-compet
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
8-Oct-1999