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`Unmasking' A Crafty Microbe

Developments to Watch


GONORRHEA INFECTS ABOUT 1 million people in the U.S. each year. Searching for a vaccine, researchers have focused on hairlike structures made of a protein called pilin that protrude from the gonococcus bacteria and attach to host cells. But the protein constantly reshuffles the set of amino acids it presents on its surface. The host never sees exactly the same pilin twice, so it can't mount an effective immune response.

By crystallizing the protein, bombarding it with X-rays, and analyzing the diffraction patterns with computers--a technique called X-ray crystallography--scientists at Scripps Research Institute in La Jolla, Calif., have produced 3-D images that show the precise arrangement of atoms in different parts of the protein. Biologists John Tainer, Katrina Forest, and Hans Parge pinpointed a region on the folded protein consisting of 20-odd amino acids that are most prone to change, which Forest calls the protein's "mask." The rest of the structure--about 140 amino acids, depending on the particular bacterial strain--remains more or less constant.

The Scripps team is now imaging pilin from different strains to confirm the mask's location. If they're right, they should be able to strip the mask away, create copies of pilin representing only the relatively constant portions, and mass-produce those as a vaccine. Since the pilin protein in gonorrhea is similar to that in meningitis and cholera, an immune response to such a vaccine could attack those bacteria as well, allowing for a 3-in-1 vaccination. But refining and testing such a vaccine could take another 10 years.EDITED BY NEIL GROSS

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