New Findings on Listeria

New discoveries about the mechanism of spread between cells of the foodborne pathogen Listeria monocytogenes could shed light on a host of other bacterial illnesses with similar patterns of infection. Listeria can cause serious illness in immunocompromised people and spontaneous abortion in pregnant women. In addition to infecting humans and animals, it can also grow on vegetables.

This means that Listeria can enter the food supply at just about any point, from the farm in infected feed, through the processing plant, to the consumer’s kitchen. The Listeria organism moves through the cell’s cytoplasm projected by a “comet tail” made of a protein called actin. When it reaches the cell membrane, it pushes through to a neighboring cell, ballooning the membrane of the infected cell out into a protrusion that is internalized by the uninfected cell.

New Findings

New research by Keith Ireton, PhD, University of Central Florida, demonstrates that Listeria overcomes tension at the cell membrane by means of InlC, a secreted protein that inactivates the host cell protein Tuba. Tuba is thought to have the function of creating tension in the cell’s plasma membrane. Once the membrane tension is released, the protrusion can form in the slackened membrane. “It’s like a finger inside a balloon … that can push into an adjacent cell, which is, at that point, uninfected,” Dr. Ireton said. “It swallows up that protrusion. The spreading process that occurs in Listeria is thought to play an important role in virulence.”

Prior to this discovery, it was thought that bacteria like Listeria spread simply by forcing their way into a neighboring cell through actin polymerization. Listeria is shielded from attack by the organism’s immune system because it spreads directly from one cell to another and spends the majority of its life cycle inside the cell shields.

Dr. Ireton’s team characterized the role of InlC in a Listeria infection by creating a strain of Listeria that lacked the InlC gene. The new strain exhibited a significantly reduced ability to spread from cell to cell or to form protrusions.

Important Implications

This discovery has important implications for other bacteria that spread via similar protrusions. Unlike Listeria, some of these organisms represent a major threat even to healthy people. “Several human pathogens undergo cell-cell spreading in a manner similar to Listeria monocytogenes, including Shigella flexneri, Burkholderia pseudomallei, and Rickettsia species,” said John Brumell, PhD, an associate professor in the department of molecular genetics at the University of Toronto. “We don’t know if the other bacteria ‘slacken’ host membranes in the same way as Listeria monocytogenes, but this will be an important issue to study.” Shigella flexneri causes a diarrheal illness, while Rickettsia is best known for causing Rocky Mountain spotted fever. If they share the mechanism of deactivating Tuba using InlC, this could become an important therapeutic target.

According to Dr. Ireton, new awareness of InlC as a virulence factor could also influence the types of polymerase chain reaction (PCR)-based tests that are performed in food processing plants. For example, PCR testing is used to detect Shiga toxin, which is a virulence factor for enterohemorrhagic E. coli. Similarly, InlC could be an indicator of more virulent strains of Listeria.

“The authors have done a detailed and impressive functional characterization of a virulence factor in Listeria whose identity has been known for some time but without any clear indication of its function,” said Nancy E. Freitag, PhD, an associate professor in the department of microbiology and immunology at the University of Illinois at Chicago College of Medicine. “Their study provides new understanding of how bacteria mediate spread from one host cell to an adjacent cell.”