UVa scientists detail salmonella protein

CHARLOTTESVILLE, Va., Sept. 25 A protein in Salmonella bacteria called SipA invades healthy human cells by using two arms in a "stapling" action, according to scientists at the University of Virginia Health System. The U.Va. researchers, working with colleagues at Rockefeller University in New York, report their findings in the September 26 edition of the magazine Science.

Edward Egelman, professor of biochemistry and molecular genetics at U.Va., said the significance of this research is that it could be possible to design molecules to prevent SipA from binding to a protein called actin, preventing the severe infection associated with Salmonella.

According to the Centers for Disease Control and Prevention, various types of the Salmonella bacteria are responsible for up to four million infections and 500 deaths in the United States every year. Salmonella can cause diarrhea, fever and abdominal cramps. Most people recover without treatment, but young children, the elderly and people with compromised immune systems are at risk for developing severe infections. There is no vaccine to prevent Salmonella-related sickness.

Egelman and his colleagues found that SipA works as a molecular "staple" and tethers itself to actin, a protein found in all human cells. SipA can polymerize actin into long filaments.

This activity may explain how this bacterial protein helps rearrange a cell's cytoskeleton, or the inner scaffold that gives a cell shape and provides motility. By remodeling the cytoskeleton of host cells, bacterial proteins such as SipA allow the Salmonella bacteria to infect these cells.

"This is a cunning evolutionary pathway that has developed with Salmonella," Egelman said. "It has the interesting property of being able to control the host actin filaments by using arms to do it. It has actually evolved, we believe, to mimic human proteins that bind to actin. This allows Salmonella to become a Trojan horse of sorts, causing heal

Contact: Bob Beard
University of Virginia Health System

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