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Bentley Leads Sanger in Attack on Whipplei

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Its genome may be puny compared to those of other organisms being sequenced, but the bacteria Tropheryma whipplei gives Stephen Bentley undeniable enthusiasm.

Bentley led the team, which included members from Sanger, Stanford, the University of Birmingham and the University of Heidelberg, to sequence T. whipplei, an intestine-dwelling bug that causes Whipple’s disease.

Whipplei didn’t go quietly, Bentley says. Though funding was approved for the project in 2001, difficulty in culturing the organism held up the work for months. Eventually, Matthias Maiwald hit upon a culture technique that worked, albeit slowly, and in 15 months had harvested enough cells for the whole-genome shotgun effort. Shotgun, assembly, finishing, and analysis went so quickly for the 926 KB genome that “the culture process took at least three times as long as the rest of the project,” Bentley says.

Very little was known about whipplei when the project began, and two key findings turned up through the sequence. First is the host-obligate nature. “There was debate about whether there was an environmental niche for this organism,” he says. “Looking at the genome we can now say that’s almost completely out of the question. … Missing lots of biosynthetic pathways, it seems as though it would be unable to survive outside its host.”

The second noteworthy finding was a new family of surface proteins that suggested “a novel mechanism to evade the immune system,” says Bentley, who joined the seven-person bacterial team at Sanger from the biochem department at Cambridge close to five years ago.

Bentley and his colleagues are already back to work on other bacteria, adding to the collection of microbes that have already been sequenced. “As genomics goes on we’ve sort of been ticking off the nasty pathogens,” Bentley says. “But now we see the value of comparative genomics” to understand the differences between pathogens and their harmless relatives, he adds.

— Fingerprints by Meredith Salisbury

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