How Salmonella Stalks Its Victims
The food-borne germ tricks its way into unsuspecting cells
THURSDAY, Sept. 25, 2003 (HealthDayNews) -- Scientists have discovered salmonella bacteria employ a Trojan horse strategy to take over and infect host cells.
This unusual look into the machinery of this sometimes deadly food-borne bacteria, courtesy of an electron microscope and other technologies, may one day help researchers design drugs to thwart this and other germs.
"This is one small component of a very big puzzle," says Ed Egelman, co-author of a paper appearing in the Sept. 26 issue of Science and a professor of biochemistry and molecular genetics at the University of Virginia Health System.
Salmonella is commonly transmitted by undercooked or uncooked food. According to the U.S. Centers for Disease Control and Prevention (CDC), about 40,000 cases of salmonella infection are reported in the United States each year, although the actual number of cases may be 30 or more times higher. Although most people recover without treatment, some 600 people die every year.
Most people infected with salmonella develop diarrhea, fever and abdominal cramps within 12 to 72 hours of infection. The illness usually lasts four to seven days. But for some people, the diarrhea may be so severe they may need to be hospitalized and treated with antibiotics, the CDC says.
Using an electron microscope along with X-ray crystallography and 3-D reconstruction, researchers at Rockefeller University in New York City and the University of Virginia managed to get the first high-resolution picture of part of the SipA protein, a key component of the salmonella bacteria's machinery.
"Salmonella secretes a number of proteins that are involved in taking control of the host cell to engulf the bacterium and in that way infecting the host cells," Egelman says. "This particular protein, SipA, is one of a number that are produced and it has been shown previously to bind to actin."
Actin is one of the most abundant proteins in the human body and is involved in the cytoskeleton -- the framework of cells -- and in cell movement. "It's like a protein scaffold that holds the cell together," he says.
Although scientists knew salmonella proteins bind to actin, they did not know precisely how this occurred.
As it turns out, SipA essentially "staples" actin into long filaments, which then reorganize the cytoskeleton of the host cell. "This reorganization causes the host cell to engulf the bacterium, something that it would not normally do," Egelman explains. "Once the bacterium is engulfed by the host cell, it can multiply within the host cells."
Contrary to scientists' expectations, SipA turned out to be compact and heart-shaped with a globular core. Two "arms" project from either side, the researchers say.
It's not yet clear how this new knowledge will translate into protective or therapeutic gains. "It's a small piece of a big puzzle, but we don't know at what point a particular piece will lead to some therapeutic agent that could block salmonella," Egelman says.
While the modification of the host actin is one of the central mechanisms of salmonella, it's again just a piece of the larger picture.
"This is just a fragment," Egelman says. "We obviously want to look at larger and larger pieces of this protein. There are other salmonella proteins that are part of the same secretion system and several of them bind to actin and we want to look at those."