Listeria monocytogenes express a surface protein, internalin, that interacts with a host receptor, E-cadherin, to promote entry into human epithelial cells.
Murine E-cadherin, in contrast to guinea pig E-cadherin, does not interact with internalin, excluding the mouse as a model for addressing internalin function in vivo.
|Listeria internalin mediates crossing of the intestinal barrier.
The researchers generated transgenic mice that expressed human E-caderin (hEcad) solely in enterocytes, and reported their findings in the 1 June issue of Science.
They placed the hEcad gene under the control of the iFABP promoter.
iFABP encodes the intestinal isoform of the fatty acid binding protein, whose expression is restricted to epithelial cells of the small intestine.
Non-transgenic mice were used as controls.
The mice were administered with either 5 × 1010 wild-type L. monocytogenes or an internalin mutant.
The team found that none of the non-transgenic mice died after oral infection with either wild-type or mutant bacteria.
However, 85% of the transgenic mice died after receiving wild-type L. monocytogenes. None died after ingesting the same dose of internalin mutant.
The group also conducted a kinetic analysis of bacterial counts in intestine and mesenteric lymph nodes, as well as immunohistochemical studies. These showed that the internalin hEcad interaction mediated invasion of enterocytes. It also mediated subsequent intravillous bacterial multiplication, abscess formation, and access to mesenteric lymph nodes, liver, and spleen.
Investigator Marc Lecuit, of the Institut Pasteur, Paris, said on behalf of his colleagues, "Internalin is a virulence factor, mediating crossing of the intestinal barrier."
"These results illustrate how relevant animal models for human infections can be generated," he concluded.