Cracking one of Salmonella’s secrets

Some Salmonella bacteria are flexible—a mouse or a monkey is as good a host as a human. But Salmonella Typhi (S. Typhi), which causes typhoid fever, is picky: it survives only in human cells. In the November 16, 2012 issue of Science, Jorge E. Galán, chair and Lucille P. Markey Professor of Microbial Pathogenesis, and postdoctoral fellow Stefania Spanò, Ph.D., explain why S. Typhi dies off inside non-human cells.

In many types of Salmonella, a protein called GtgE keeps a group of enzymes away from the vacuole, a membrane that surrounds the bacteria inside host cells. But S. Typhi lacks GtgE, and in non-human cells the membrane becomes studded with these enzymes, including one called Rab32. In mouse immune cells Rab32 delivers antimicrobial factors to the S. Typhi-containing vacuole, but in humans, “the immune system is still firing bullets, but this pathogen has learned how to dodge them,” Galán says. When the scientists blocked Rab32 or added the GtgE gene to S. Typhi, the bacterium successfully infected mice for the first time, results that could lead to new treatments for typhoid fever.