He's been surprised at the results. "We've found that the host cell is clearly not an innocent bystander," says Falkow. "It actually participates by ushering in the bacteria."

For instance, in the early stages of a Salmonella infection, a single bacterium enters a killer cell, called a phagocyte. Phagocytes are cells in our immune system that destroy foreign invaders. Once inside, however, the Salmonella tricks the phagocyte into reaching out with special structures called ruffles and pulling more Salmonella bacteria in from the outside. You almost have to admire the bacteria's brash approach: they go straight to the most dangerous cells in the immune system and then, like tiny Trojan horses, get the cell to open up and pull them in.
Once inside the phagocyte, the bacteria are enveloped in a membrane-walled "room" called a vacuole. At this point, most invaders are doomed: the phagocyte normally injects proteins into the vacuole to dissolve the bacteria. Some Salmonella, however, manage to protect themselves by preventing the host cell from dispatching these toxins. How they manage this is a mystery.

"If I knew the answer," says Falkow, "I could maybe get a Nobel Prize."

Ruffling

Salmonella trick the immune cell into reaching out and pulling them inside. Video provided by Stanley Falkow. 2.4 Megabyte QuickTime Movie. Click on the image to view.

Falkow continues: "We know a little bit. We certainly know that something is happening genetically and biochemically in one compartment and not another."

Eventually, the bacteria reproduce until they fill up the vacuole. Then they subvert the host again by sending out a protein which sets off a chain of biochemical reactions that eventually leads to the death of the host cell.



Stanley Falkow, Professor of Microbiology and Immunology at Stanford University Medical School and incoming president of the American Society of Microbiology, began a lifelong fascination with bacteria when he was 11 years old. He has devoted his academic career to understanding the complex interactions between pathogenic microbes and their human hosts. To complement the Exploratorium's current special exhibition, Hidden Kingdoms, Professor Falkow sat down with writer Mary Miller and provided a rare peek at how microbes invade our cells.

Stanley Falkow explains, "Why he likes bacteria more than people" 
The RealAudio clip that appears here is the first of three that appear in this story.
14.4/28.8/RealAudio

Microbe Spy

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