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by Laura Spinney
A model bacterium is showing scientists how pathogens go from harmless to deadly.
In the early 1980s, scientists needed a model microbe they could use in the fight against infectious bacteria. Tuberculosis was re-emerging as a global health problem and a similar bacterium—one that also invades host cells—had been identified as the cause of Legionnaire's disease.
Enter Pascale Cossart. Then a young postdoc at the Pasteur Institute in Paris, Cossart was encouraged by her mentor, molecular biologist Maxime Schwartz (who would later become director of the institute), to leave her comfort zone—the study of gene-protein interactions—and investigate the more “pasteurian” theme of infection. It was a big jump for Cossart, a biochemist by training, but she soon realized that the infectious agent she had chosen to study, Listeria monocytogenes, could be the model everyone was seeking.
Listeria grows quickly and has both benign and disease-causing varieties, so she could study virulence by comparing the two. It also behaves similarly to other disease-causing, intracellular bacteria, such as Chlamydia and Rickettsia, as well as Legionella and Mycobacterium tuberculosis.
Over the last two decades, Cossart, an HHMI international research scholar who heads the Pasteur Institute's Unit of Bacteria-Cell Interactions, has helped make Listeria one of the best understood bacterial pathogens. In 1996, for example, with Jérême Mengaud, also at the Pasteur Institute, she identified the human protein E-cadherin as the receptor that Listeria latches onto, allowing it to enter host cells. Listeria's genome sequence was completed in 2006 thanks to an international consortium that Cossart coordinated. The methods her group has developed for studying Listeria are being applied more widely—for instance, their transgenic mouse model of Listeria infection is now also regarded as a model for viral and parasitic infections.
Most recently, Cossart's group has created a map showing how the transcriptional products of Listeria's genome change when the bacterium exists under different environmental conditions. The work appeared in Nature on June 18, 2009.
When ingested in contaminated food, Listeria can trigger miscarriage and kill people with weakened immune systems. It has the unique ability to invade three internal barriers: the intestinal lining, the placenta, and the blood-brain barrier. Cossart's latest findings may begin to explain how it transforms from a benign, free-living microbe into a dangerous agent of disease.
As a basic scientist, Cossart also wonders if the new map might give insight into how other opportunistic pathogens make that switch too. “For me, [Listeria] is a platform on which I establish concepts that I can then investigate in other pathogens, to see if they behave like it,” she says.
Illustration: Ritchie Stirling / Hulton Archive / Getty Images