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Food safety: French discovery explains how Listeria penetrates the body, and may suggest new drug delivery strategies

e to enter the bloodstream, where it disseminates to the central nervous system and the placenta. But, the molecular events that allow Listeria to cross the intestinal barrier have remained a mystery--until now.

In previous studies, Cossart and her colleagues--including Jean Louis Gaillard, Jerme Mengaud and Marc Lecuit--had shown that a protein on Listeria's surface called "internalin" interacts with a receptor, E-cadherin found on cultured cells derived from the intestine. Similar to a key-and-lock system, internalin interacts with E-cadherin to promote the entry of Listeria into intestinal cells. Listeria can then cross the intestine and pass into the bloodstream, scientists said.

Studying this mechanism in animals proved difficult, however, because rats and mice produce a form of cadherin that doesn't bind with internalin. Fortunately, guinea pigs generate a suitable version of the protein, making these animals a useful model for studying oral Listeria infection. The difference between the two forms of cadherin, Cossart explained, is a single amino acid in the 16th position of cadherin's molecular chain.

For their latest Science study, Lecuit et al.(Cossart's team in collaboration with transgenesis expert Charles Babinet and other scientists at the Pasteur Institute), investigated oral infection mechanisms within guinea pigs and transgenic mice, which had been genetically modified to express the human version of cadherin in the intestine. Animals received oral doses of both wild-type Listeria, as well as a mutant, internalin-free version of the bacterium. Wild Listeria, featuring the internalin protein, proved fatal in most cases, whereas the mutant strain caused no deaths and failed to cross the intestine and invade organ tissues.

Thus, the French investigation identifies a "virulence factor" or molecular mechanism by which Listeria causes disease, thereby addressing a key recommenda
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Contact: Ginger Pinholster
gpinhols@aaas.org
202-326-6421
American Association for the Advancement of Science
31-May-2001


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