"We had expected to see PIP2 and PIP3 only at the very back of Listeria where new actin assembly was taking place," recalls Dr. Southwick. "To our surprise these lipids also localized to the front of the moving bacteria." The researchers also noticed that Listeria movement slowed down when the bacteria were treated with molecules that inhibited PI3-kinase, proving that Listeria depend on PI3-kinase to move.
"Our studies show that Listeria is capable of inside-out signaling," explains Dr. Southwick. "Most signals arise from molecules binding receptors on the outside of the cell. In the case of Listeria, we find that this intracellular pathogen can harness signals from the inner rather than the outer surface of the cell membrane.
"The most exciting and surprising finding is that an intracellular bacteria is able to attract host cell membrane lipids to its surface and these membrane lipids facilitate the ability of the bacterium to move within cells. This capability is unique to Listeria and is not found in another intracellular bacteria, Shigella. Our experiments show that Listeria is a simplified model system for studying how phosphoinositides regulate the actin cytoskeleton, and this model promises to yield additional insights into how these phospholipids control the cell's actin cytoskeleton. Our discoveries provide additional fundamental clues as how cells move."
These findings may also open the door to using PI3-kinase inhibitors or other agents that lower PIP2 and PIP3 levels to slow the spread of Listeria and control infection in patients who are not responding to antibiotics, although that application is a long way off, says Dr. Southwick.