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Scientists discover that host cell lipids facilitate bacterial movement

When the bacterium Listeria monocytogenes invades the body, it commandeers its host cell's actin cytoskeleton to invade other cells. In a report published in the Journal of Biological Chemistry, a group of scientists provide insight into the molecular mechanisms behind this infection technique.

The research appears as the "Paper of the Week" in the March 25 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Listeria causes a variety of diseases, the most severe being meningoencephalitis, an inflammation of the brain and the membranes that envelop the brain and spinal cord. Infection begins when the bacterium binds to a receptor on the surface of a cell, causing the cell to ingest it. The bacterium multiplies inside the cell and then uses a cellular protein called ActA to stimulate the host cell's actin to form filaments at one end of the bacterium.

"As these filaments lengthen, they drive the bacterium through the cell until it reaches the peripheral or outer cell membrane," explains Dr. Frederick Southwick of the University of Florida College of Medicine. "Here the growing actin filaments push the bacterium against the membrane, forming long membrane projections called filopodia. These filopodia push into adjacent cells and are ingested by them. The bacteria then enter the new cell and begin the cycle anew. Essentially Listeria takes over or hijacks the host cell's actin cytoskeleton to move within cells, and to spread from cell to cell."

In most cells, two membrane lipids, PIP2 and PIP3, are associated with the formation of new actin filaments. PIP3 is synthesized from PIP2 by an enzyme called PI3-kinase. The lipids attract and modify the functions of proteins involved in regulating actin assembly. PIP2 and PIP3 also prevent capping proteins from binding to the ends of actin filaments, allowing new actin filament assembly.

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Source:American Society for Biochemistry and Molecular Biology


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