Listeria bacteria reveal secrets to spreading infection

By Robert Sanders, Public Affairs

08 NOVEMBER 00 | Many deadly microbes have learned that the key to launching an infection is not to kill your host - at least not too quickly.

Now, scientists at Berkeley, have discovered how one microbe, Listeria monocytogenes, is able to manage this.

In a paper in this latest issue of Science, Daniel Portnoy, professor of molecular and cell biology in the College of Letters & Science and professor of infectious diseases in the School of Public Health, along with post-doctoral fellow Amy Decatur, describe the trick these bacteria use to live comfortably inside a cell until they're ready to break out and spread the infection to other cells.

The finding could have implications beyond this one bacteria, which causes a deadly disease called listeriosis. The world's top three infectious killers - AIDS, tuberculosis and malaria - all are caused by pathogens that ensconce themselves snugly inside cells and live to wreak havoc. Yet, these intracellular pathogens have been hard to study, Portnoy said.

"There are no effective vaccines for any of these diseases, in part because it is difficult to study intracellular pathogens," he said. "Listeria is a great model system for studying the host-pathogen interaction of these intracellular bugs."

Listeria is a common but deadly bacterium that in recent years has made headlines as a contaminant of hot dogs, cheese, cole slaw and other foods, causing more than two thousand infections every year and 500 deaths. Though it hits immune-compromised people hardest, its overall fatality rate is about 20 percent.

Listeria bacteria establish an infection by inducing immune-system cells, to corral and swallow them, so that they end up encased in a bubble within the body of the cell. The bacteria would be benign if they remained isolated in the vacuole, because the cell can kill them there. But they eventually break out with the help of a pore-forming toxin and take over the host cell's machinery to spread the infection.

A big question has always been why the toxin, listeriolysin O, doesn't also rupture and kill the cell, exposing the bacteria to the immune system.

Several years ago, a post-doctoral fellow in Portnoy's lab compared listeriolysin O to a similar pore-forming toxin called perfringolysin O, from the extracellular bacteria that causes gangrene. Sian Jones and Portnoy found that if they substituted perfringolysin O for Listeria's normal toxin, the altered bacteria were able to punch their way out of a vacuole, but then they killed the host cell. This made Listeria totally avirulent, Portnoy said, because the immune system efficiently mopped up the exposed bacteria.

"It's a great example of how bacteria have taken advantage of the host's biology to enhance their pathogenicity," Portnoy said.