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Anti-Immune Trick Unveiled in Salmonella

19 July 1999 7:00 pm
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Researchers may have found the reason why patients with a systemic Salmonella infection, such as typhoid fever, are slow to quell the infection and get very sick. In the current EMBO Journal, they report that some Salmonella species can create an intracellular traffic jam within certain of the host's immune cells, which protects the bacteria from being killed.

Immune cells such as macrophages normally kill bacteria by first encircling them with the cell membrane, forming a vesicle within the cell. The vesicle eventually docks with a lysosome--a death chamber where toxic chemicals and enzymes chew up the cargo. Some studies have suggested that Salmonella can survive passing through the lysosome, while others indicated that the organism manages to avoid them altogether. In search of more clues, microbiologist Eduardo Groisman of the Washington University School of Medicine in St. Louis and colleagues focused on an unusual gene they had previously identified, spiC. The team created a mutant strain that doesn't produce the SpiC protein and found that it grows poorly in macrophages and is much less virulent in mice than are wild-type bacteria, suggesting that the protein is central to Salmonella's harmful effects.

In another experiment, the team showed that wild-type Salmonella were less likely to end up in the lysosome than were SpiC mutants. And when they used radioactively labeled molecules to monitor vesicle traffic, they found that even for vesicles that didn't contain Salmonella, transport seemed to be inhibited in cells infected with wild-type bacteria, whereas lysosomes received their usual deliveries in cells infected by SpiC mutants.

Other bacteria trapped in vesicles have evolved ways to prevent their compartment from fusing with the lysosome, but SpiC, the team concludes, is the only bacterial protein known to tie up global vesicular traffic. Just as one crucial accident can slow activity throughout a city, SpiC's traffic snarl may have profound effects on its host cell.

"This is a totally new way of altering trafficking," says Jorge Galán, a microbiologist at Yale University. "It points at a mechanism that's very different from that of any other bug. ... It has to be interfering with some key regulator of the trafficking pathway."

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