Listeria hijacks transport machinery to invade cells

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Related tags: Listeria, Bacteria, Protein

New fundamental science reveals how the major foodborne pathogen
Listeria monocytogenes commandeers cellular transport
machinery to invade cells and hide from the body's immune system.

French scientists detail how Listeria invades cells by activating cellular machinery that transports viruses, small molecules, and proteins. Once it has safely entered a cell, the microbe can replicate and continue the process of infection.

Food safety is a leading issue in society today, made ever more urgent by the growth of mass food production and the increasing incidence of foodborne pathogens, engendering heavy costs to industry, employer and government.

Although infections caused by listeria are not as common as for salmonella, they can cause anything from diarrhoea to blood poisoning or meningitis, just as the bacterium can lead to miscarriages or cause disease in foetuses and newborns.

Food safety experts estimate that 100 to 1,000 cells can cause the illness.

Food makers are required to test each food batch where the harmful pathogen Listeria monocytogenes may be present, such as soft cheese and processed meat products, and in particular those kept refrigerated for a long time where the pathogen can grow at low temperatures.

Cooking kills most of the L. monocytogenes cells that can grow at refrigeration temperature, but ready-to-eat products, such as fermented sausages, and smoked fish, are not always cooked by consumers before consumption.

New research conducted by Pascale Cossart, at the Howard Hughes Medical Institute, and her colleague Esteban Veiga at the Institut Pasteur in Paris, details how Listeria invades cells by activating cellular machinery that transports viruses, small molecules, and proteins.

Once it has safely entered a cell, the microbe can replicate and continue the process of infection.

The body usually deals with bacteria and other large, foreign microbes through a process called phagocytosis. Specialised cells engulf the invading microbe and destroy it.

Scientists long believed that cells use a second process, called endocytosis, to deal with smaller molecules or viruses. In endocytsosis, a cell's outer membrane pinches inward around the target to form a pocket that's brought inside the cell, creating a structure called a vesicle.

"Phagocytosis and endocytosis may, in fact, be more similar than past research suggests. This is a totally new concept,"​says Cossart.

Cossart's lab had observed that Listeria - which is 20 times the size of the largest particle scientists believed a cell could take in by endocytosis - could invade non-phagocytic cells.

Other labs had made similar observations with other bacteria. Cossart and Veiga investigated the underlying machinery behind this uncommon invasion strategy, which they knew depended on an interaction between a protein on the surface of the bacteria, known as InlB, and a protein called Met on the surface of the cell it was invading.

They discovered that when InlB interacts with Met, the cell responds by adding a chemical tag to Met that flags it for protein recycling or degradation.

Since Met is on the outside surface of the cell and the recycling and degradation machineries are inside, the cell must bring Met inside through endocytosis in order to dispose of it. As the cell creates the vesicle that will transport tagged Met, Listeria stows away and invades the cell.

By manipulating the gene expression of the cells Listeria was invading, the researchers showed that specific molecules known to be 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 infect hosts, according to Cossart, suggests that other bacteria may exploit the same mechanism to gain entry into non-phagocytic cells.

"This mechanism of cell entry may be used by several different kinds of bacteria, which is a major deviation from the belief that endocytosis is strictly for importing small molecules into cells,"​ she adds.

Full findings are published in the 21 August 2005, issue of Nature Cell Biology.

Related topics: Science

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