Sugar coated: molecular dress-up may disguise gut bacteria

Science News, March 19, 2005 by C. Brownlee

Even when you think you're alone, you're not. Several trillion bacteria tag along within the intestines of a typical person or other mammal.

While researchers have long known that these bacteria serve beneficial functions for their hosts, such as producing vitamins and breaking down nutrients (SN: 5/31/03, p. 344), it hasn't been clear why the host's immune system doesn't attack the microbes as foreign invaders. A new study suggests that these bacteria disguise themselves with sugar molecules originating in their host's intestinal cells.

Many scientists have theorized that gut bacteria use such molecular mimicry to avoid immune system detection. However, the researchers lacked convincing data. Seeking new evidence, Laurie E. Comstock and her colleagues at Harvard Medical School in Boston examined Bacteroides fragilis, a common gut bacterium.

The team knew that B. fragilis internally produces a simple sugar called fucose, which it attaches to proteins on its surface. Previous studies had shown that the bacterium also induces intestinal cells in its host to secrete fucose. Researchers had presumed that the bacteria use this external fucose as fuel.

Making fucose from the sugar mannose is common in bacteria, including B. fragilis. Mammalian cells, in contrast, convert fucose from their surroundings into a form called guanosine diphosphate-fucose (GDP-fucose), which they attach to their surface proteins. No bacterium had been observed performing such a conversion.

Comstock's team created a strain of B. fragilis lacking the gene that directs the conversion of mannose to fucose, then the researchers grew the bacteria on a nutrient-rich medium containing both sugars. They predicted that the bacteria would not attach fucose to their surface proteins.

The microbes did it anyway. Further investigation showed that B. fragilis was using an enzyme, never before seen in bacteria, to convert the fucose from the medium into GDP-fucose. The bacteria then decorated their surfaces with the host fucose, just as intestinal cells do.

"Here we have an organism living in close association with us that has coevolved in the intestine [altering a sugar via] a mammalian-like pathway," says Comstock.

The researchers located the bacterial gene that converts fucose to GDP-fucose and then created a mutant strain of B. fragilis missing that gene. When the team fed mice equal amounts of these mutant bacteria and normal ones, the animals' stools within 2 days contained only normal B. fragilis.

Comstock says in the March 18 Science that dressing up in a host's fucose may give B. fragilis a competitive advantage in colonizing the intestines.

Although Comstock's findings don't prove that this advantage protects the bacterium from detection by the mammalian immune system, they "strongly suggest it," says Lora Hooper of the University of Texas Southwestern Medical Center in Dallas.

It remains to be established, notes Hooper, whether a mutant B. fragilis that can't convert fucose into GDP-fucose instigates an immune system attack.