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Scientists dissect bacterial crosstalk

St. Louis, Aug. 20, 1999 -- Please pass the sugar, a hungry bacterium says. And the lining of the intestine complies. But how can microbes talk to mammals' With a dual-purpose protein, scientists find.

The microbes in our body -- more numerous than human cells -- fend off pathogens and do other essential chores. "But we know very little about how our relationships with them are forged," says Jeffrey I. Gordon, M.D. "We want to understand the conversations that occur between these microbial guests and their host."

The findings appear in the Aug. 17 Proceedings of the National Academy of Sciences. Gordon, the Alumni Professor and head of molecular biology and pharmacology and professor of medicine at Washington University School of Medicine in St. Louis, is senior author of the paper. Postdoctoral fellow Lora V. Hooper, Ph.D., is first author.

Four hundred species of microbes call our gut home, competing for space and food. To cut through the cacophony, the researchers studied just one species.

Bacteroides thetaiotaomicron lives in the lower part of the gut and feeds on a sugar called fucose. It arrives early in a mammal's life, paving the way for other friendly microbes.

Using germ-free mice, Gordon's group previously showed that cells lining the intestine make fucose, posting the sugar on the cell surface. At weaning, fucose production stops. But it starts up again if mice are exposed to B. thetaiotaomicron. So the bacterium somehow tells the intestine to give it food. And the researchers have found the molecular switch.

First, Hooper created mutants of B. thetaiotaomicron that were unable to utilize fucose. Analyzing these strains, she identified five genes in a row that shared a regulatory region.

Four were involved in fucose uptake or metabolism. But the first coded for a repressor protein, FucR. Hooper purified the repressor and studied FucR mutants. She deduced that the protein halts the transcription of the five genes
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Contact: Linda Sage
sage@medicine.wustl.edu
314-286-0119
Washington University School of Medicine
20-Aug-1999


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