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Salmonella uses molecular staples to change structure of infected cells

Salmonella, a well-known food-borne bacterium, uses protein "staples" to restructure the shape of the gut cells it invades, forcing these cells to flow around the bacteria and engulf them, researchers at Rockefeller University have discovered.

The research, published in the September 26 issue of the journal Science, provides the first detailed insight into how bacteria physically manipulate host cells at the onset of an attack. The findings may help scientists develop a more general understanding of similar strategies used by a diverse array of deadly bacteria and lead to improved drugs for fighting them.

Collaborating with researchers at the University of Virginia Health Sciences Center, the Rockefeller team found that Salmonella injects proteins into host cells that staple together molecules of actin, the scaffolding protein that provides structure to a cell. Like welding girders to each other to construct a skyscraper, Salmonella proteins tack actin into long filaments that expand the size and change the contour of a cell so it can fold itself around the bacterium.

The protein that staples actin together - the Salmonella invasion protein A (SipA) - is unlike any molecule found in the human body, the researchers say.

"No protein in our cells is quite as potent, or elegant, as SipA," says the lead author, Assistant Professor C. Erec Stebbins, Ph.D., head of the Laboratory of Structural Microbiology at Rockefeller University. "One small protein is able to go into a host cell, hijack its biochemistry and rearrange its structure. That's a powerful example of host-pathogen co-evolution."

"Erec Stebbins and his colleagues have made a crucial discovery that may lead to the development of better drugs to treat this major threat to human health and well-being," says Rockefeller University's new president, Paul Nurse, Ph.D.

The research helps complete the picture of what happens when Salmonella infects the human intestinal t
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
25-Sep-2003


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