Just as the police will try to reconstruct every detail of a crime, medical detectives seek to explain how bacteria cause illness, step by step. One unsolved case has been that of Listeria monocytogenes, which causes severe and sometimes deadly food poisoning. But in today's issue of Science, Pascale Cossart and her colleages at the Pasteur Institute in France reveal a secret to Listeria's unhealthy acts of breaking and entry. In particular, they have discovered precisely how the organism passes from the digestive track into intestinal cells, thereby gaining access to the bloodstream and ultimately the central nervous system.
Earlier work implicated a molecule called internalin, found on the surface of Listeria cells. In humans, this molecule binds to E-cadherin receptors on cells derived from the intestine. The researchers assumed that internalin, like a key, provided access to the intestinal cells, but the mechanism was hard to study because in mice E-cadherin does not interact with internalin. So the scientists genetically engineered mice that produce human E-cadherin and also ran tests on guinea pigs, which produce a version that binds to internalin.
The team exposed both types of animals to wild-type Listeria and to a mutant form lacking internalin. They discovered that whereas the wild-type bacteria proved fatal in most cases, the mutant type failed to enter intestinal cellsproving that internalin is essential for infection. "This is a very tricky bacterium," Cossart says. "For the moment, most people are reasonably safe because the bacterium is sensitive to antibiotics. If it becomes resistant, as we have seen with other bacteria, then it will be critical to know precisely how the infection proceeds in order to design new therapeutic strategies."
