October 4, 2010

Salmonella Are Armed, Agile and Primed for Invasion

Microscopic image shows a clump of red, rod-shaped bacteria Rapidly replicating Salmonella bacteria (red rods) inside epithelial cells that line the gut. These bacteria are primed for infection. NIAID/Rocky Mountain Laboratories.

Scientists have discovered a subset of Salmonella bacteria that are fast-replicating, quick-moving and apparently armed with a needle-like complex that can penetrate cells in the human gut. The findings may help explain how Salmonella, a common cause of food poisoning, can spread so efficiently.

Salmonella sickens an estimated 40,000 people nationwide each year, according to the U.S. Centers for Disease Control and Prevention. The actual number is likely much higher, because many mild cases aren’t diagnosed or reported. The bacteria have been making headlines in recent weeks, after the recall of more than a half-million possibly contaminated chicken eggs and the launch of an ongoing U.S. public health investigation.

When Salmonella invade the epithelial cells that line the intestines, the bacteria survive and replicate inside unique membrane-bound compartments called vacuoles. But while much is known about how the bacteria invade intestinal cells, scientists have yet to understand how the bacteria can move between cells or back into the gut to spread. 

To learn more, a research team led by Dr. Olivia Steele-Mortimer of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) took a closer look at Salmonella to see how it might spread from cell to cell or from person to person. The investigators used high-resolution confocal microscopy to examine lab-grown epithelial cells similar to those that line the human gut. The cells were infected with Salmonella enterica, a common cause of gastrointestinal infections. The results appeared in the September 27, 2010, early online edition of the Proceedings of the National Academy of Sciences.

About 4 hours after infection, the researchers observed a population of rapidly reproducing Salmonella that wasn’t confined within a vacuole but instead moved freely within the cells. In contrast to vacuolar Salmonella, these fast-replicating Salmonella have flagella—long whip-like projections for mobility—and express genes for a “needle complex” that the bacteria use to invade cells. With these attributes, this population of Salmonella is well prepared to spread and invade new cells.

The scientists found that cells containing the hyper-replicating, invasive Salmonella are quickly pushed out of a simple layer of lab-grown cells, resulting in the release of bacteria, and that a similar process occurs in the epithelial layers of infected mice. The process resembles the natural mechanism for shedding dying epithelial cells from the intestinal lining. But unlike the normal shedding mechanism, the Salmonella-induced process is followed by an immune response that includes release of the protein interleukin-18. This protein sets off an inflammation cascade, which provides an explanation for the acute intestinal inflammation associated with Salmonella infections.

“Unfortunately, far too many people have experienced the debilitating effects of Salmonella, which causes disease via largely unexplained processes, including overactive inflammatory responses,” says NIAID Director Dr. Anthony S. Fauci. “This elegant study provides new insight into the origins of that inflammatory disease process.”

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