Salmonella uses molecular staples to change structure of infected cells

ract - which it does frequently. Worldwide, Salmonella bacteria cause more than one billion new human infections each year, resulting in more than three million deaths. Most infections are due to errant consumption of food contaminated with animal feces, but because Salmonella has also been used as a biological weapon, the pathogen is classified as a food and water safety threat in biodefense by the National Institutes of Health.

Stebbins and his colleagues are among the first researchers to study the intricate interactions that occur between infectious microbes and host cells at the molecular level. Using techniques adapted from biochemistry, microbial cell biology and structural biology, Stebbins is developing a library that will detail the molecular composition of proteins, known as "virulence factors," that bacteria employ to infect host cells and use its biochemical machinery to replicate.

"Bacteria ranging from plant pathogens to the plague share a virulence system that is quite similar to the one Salmonella uses to gain entry into cells," he says. These bacteria use a protein "secretion system" called "type III" or "contact dependent" to inject virulence factors directly into host cells. "Bacteria have a whole armament of very sophisticated virulence proteins, and each pathogen can use these proteins in different combinations to manipulate a host cell in unique ways," says Stebbins.

The system used by Salmonella, which has been described as a "molecular syringe" with a needle attached, is one of the most complex protein secretion systems discovered, Stebbins says. Once Salmonella attaches to a cell in the gut it wants to invade, it uses the syringe and needle system to inject virulence factors into the host cell.

Researchers knew that SipA, one of the proteins injected into the host cell, could force actin proteins to join together into a strong filament that rearranged the cell's structure, but the way in which it did that wa

Contact: Joseph Bonner
Rockefeller University

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