Listeria monocytogenes Exploits Host Caveolin for Cell-to-Cell Spreading
This week we profile a recent publication in mBio from the laboratory of Dr. Julian Guttman (pictured) at Simon Fraser University.
Can you provide a brief overview of your lab’s current research focus?
My lab is generally interested in understanding how host cells are hijacked by bacterial pathogens. Currently we’re concentrating on understanding how a variety of bacteria enter human cells and spread from one cell to another to colonize organs and breach tissue-based barriers within our bodies.
What is the significance of the findings in this publication?
Once Listeria bacteria have entered a cell, these microbes hijack the host cell’s actin filament polymerization machinery to generate a rocket-like structure at one end of the bacteria. These rocket-like structures enable the bacteria to move within the cell. These structures are also used by the bacteria to push against the plasma membrane, forming a bacterially-led protrusion that pushes into a corresponding invagination in the neighbouring cell to enable the cell-to-cell transfer of the microbes. It is this type of movement that enables the bacteria to colonize entire organs and break through the placental barrier to infect the developing fetus in pregnant women.
Although the bacterial protrusions press into the neighbouring cells, this is not enough to allow for the bacteria to enter those neighbouring cells. We found that those adjacent cells use caveolin-mediated endocytic mechanisms to pull the bacteria and their rocket tails into themselves as cells depleted of caveolin or other caveolin-associated components were defective in bacterial dissemination.
What are the next steps for this research?
There must be factors on the surface of the Listeria protrusions that are used to trigger the caveolin-based internalization process in neighbouring cells. Our next step is to identify those protrusion components. We are also interested in identifying any bacterial components that are involved in the bacterial dissemination process.
Other bacterial pathogens are proposed to use similar cell-to-cell spreading mechanisms. It would be interesting to see if they also hijack the caveolin machinery for those purposes.
This work was funded by:
Funded by NSERC and SFU Department of Biological Sciences funds.