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Hide And Seek: Researchers Discover A New Way For Infectious Bacteria To Enter Cells

French scientists have learned how Listeria monocytogenes,which causes a major food-borne illness, commandeers cellular transportmachinery to invade cells and hide from the body's immune system. Theybelieve that other infectious organisms may use the same mechanism.

The Listeria bacterium, found in soil and water, can betransmitted to humans via undercooked and unpasteurized food, causingflu-like symptoms or gastrointestinal distress. For individuals withweakened immune systems, listeriosis can be fatal, and infectionsduring pregnancy can lead to miscarriage, stillbirth, prematuredelivery, or infection of the newborn.

The research was conducted by Pascale Cossart, a Howard HughesMedical Institute international research scholar, and her colleagueEsteban Veiga at the Institut Pasteur in Paris, and will be publishedin the August 21, 2005, issue of Nature Cell Biology. Cossart and Veiga detailed how Listeriainvades cells by activating cellular machinery that transports viruses,small molecules, and proteins. Once it has safely entered a cell, themicrobe can replicate and continue the process of infection.

The body usually deals with bacteria and other large, foreignmicrobes through a process called phagocytosis. Specialized cellsengulf the invading microbe and destroy it. Scientists long believedthat cells use a second process, called endocytosis, to deal withsmaller molecules or viruses. In endocytsosis, a cell's outer membranepinches inward around the target to form a pocket that's brought insidethe cell, creating a structure called a vesicle.

"Phagocytosis and endocytosis may, in fact, be more similarthan past research suggests. This is a totally new concept," Cossartsays.

Cossart's lab had observed that Listeria -- which is 20times the size of the largest particle scientists believed a cell couldtake in by endocytosis -- could invade non-phagocytic cells. Other labshad made similar observations with other bacteria. Cossart and Veigainvestigated the underlying machinery behind this uncommon invasionstrategy, which they knew depended on an interaction between a proteinon the surface of the bacteria, known as InlB, and a protein called Meton the surface of the cell it was invading.

They discovered that when InlB interacts with Met, the cellresponds by adding a chemical tag to Met that flags it for proteinrecycling or degradation. Since Met is on the outside surface of thecell and the recycling and degradation machineries are inside, the cellmust bring Met inside through endocytosis in order to dispose of it. Asthe cell creates the vesicle that will transport tagged Met, Listeria stows away and invades the cell.

By manipulating the gene expression of the cells Listeriawas invading, the researchers showed that specific molecules known tobe involved in endocytosis were essential for successful invasion by Listeria. Similarly, they found that an enzyme that tags proteins for recycling was also required.

Listeria's use of receptor-mediated endocytosis to infecthosts, according to Cossart, suggests that other bacteria may exploitthe same mechanism to gain entry into non-phagocytic cells. "Thismechanism of cell entry may be used by several different kinds ofbacteria, which is a major deviation from the belief that endocytosisis strictly for importing small molecules into cells," she says.

Source Howard Hughes Medical Institute, August 2005

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