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Wake Forest Scientists Help Discover Genetic Switch in E. coli Bacteria

Scientists at Wake Forest University School of Medicine and Harvard Medical School have uncovered backup protection that allows infectious bacterial cells to continue reproducing even when the usual recycling mechanism becomes disabled.

The investigators are studying E. coli, the bacteria implicated in illnesses following consumption of improperly cooked meat, and recently implicated in urinary tract infections.

They report in today''s (Oct. 5) issue of Science that the enzyme in E. coli that usually wards off attacks by hydrogen peroxide is turned, by a genetic switch, into an enzyme to assist the cell in the critical process of recycling other enzymes such as those needed for cell division.

The research team, headed by Jon Beckwith of the Department of Microbiology and Medical Genetics at Harvard Medical School, and including Leslie B. Poole and C. Michael Reynolds of the Department of Biochemistry at Wake Forest, said the switch, which is reversible, means that a single enzyme actually has two forms with substantially different activities.

"Although a similar sort of genetic switch has been linked to human disease, this is the first instance where such a switch operates reversibly to flip between two different functional forms of an enzyme," said Poole.

The team studied a special strain of the bacteria E. coli that grows extremely poorly because two genes had been knocked out, robbing it of the ability to recycle certain essential enzymes including several needed for cell division.

Fighting hydrogen peroxide is essential when the E. coli bacteria invade the human body. The human immune system - particularly its white blood cells -- tries to get rid of the bacteria by producing hydrogen peroxide and other peroxides, which can damage just about all components of bacterial cells. (This is why hydrogen peroxide is applied directly on wounds.)

The E. coli ordinarily fights back by producing the peroxiredoxin, an antioxidant enzyme that detoxifies hydrogen peroxide and other compounds containing peroxide. But the cells come under a different kind of stress when the recycling mechanism necessary for reproduction breaks down. That''s when the switch is thrown.

The same pattern is found in a number of other bacteria that invade people, such as Salmonella and Shigella. The research team said this commonality raises the possibility "that this change represents an evolutionarily significant advantage for these bacteria."

Poole said they were using E. coli because it is already the most widely studied of all bacteria. "Though the genetic switch has been demonstrated in bacteria in this report, the switch between enzyme forms may be a common phenomenon in higher organisms as well."

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