Protective protein

Discovery explains how bacteria tolerate foreign DNA

A protein in bacteria acts as a kind of “immune system” to protect the microbes from foreign DNA, new research shows.

The discovery suggests a way to improve yields from bacteria engineered to contain human genes for useful substances like growth hormone or insulin. It has become common to use engineered bacteria, such as E. coli, to mass produce useful proteins. Muting the activity of this protective protein, called Rho, could boost the activity of these foreign genes, some scientists suggest.

“If you can compromise Rho function without negatively impacting bacteria growth, you could improve gene expression” of inserted genes, says researcher Evgeny Nudler of the New York University School of Medicine. When Nudler and his colleagues used an antibiotic to block Rho in bacteria that had naturally acquired some foreign genes, the production of proteins by those genes increased by more than a dozen-fold.

But other scientists are skeptical that inhibiting Rho would make a difference for inserted genes, or transgenes. “It’s possible that there could be an indirect effect, but it’s unlikely that loss of Rho would have any direct effect on expression of transgenes,” says research team member Max Gottesman of ColumbiaUniversityMedicalCenter in New York. Gottesman points out that scientists usually tailor human genes for expression in bacteria before inserting those genes into the microbes, so Rho might not recognize those genes as foreign in the first place.

Whether or not the discovery proves useful for biotechnology, it helps explain how bacteria can tolerate having so much outside DNA.

Unlike plants and animals, bacteria are promiscuous with their genes, frequently swapping bits of DNA between individuals in a process called horizontal transfer. Sometimes this swapping allows a microbe to acquire a trait quickly, but often the foreign DNA is damaging or deadly to the microbe. Antibiotics that block Rho typically cause microbes to die.

Nudler’s team used a strain of the bacterium E. coli that has had most of its outside DNA removed, which enables the microbes to survive Rho-blocking antibiotics such as bicyclomycin. When the researchers exposed the microbes to the antibiotic, activity of the remaining foreign genes jumped up dramatically — in some cases as much as 100 times, the team reports in the May 16
Science .

“People were aware of Rho activity for a long time, but nobody knew until now to what extent it influences expression and what genes are affected,” Nudler says. “The genes that are affected the most are the foreign genes, the recently acquired ones.”

“That’s a new idea, definitely,” comments Jeffrey Roberts, who discovered Rho in 1969. The research “actually makes it clear what the global role of Rho is,” says Roberts, a molecular biologist at CornellUniversity in Ithaca, N.Y.

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