Versatile Bacteria Toxin
How Pathogens Manipulate Host Cell Membranes for their Own Purposes
Some aggressive bacteria are capable of penetrating human body cells and then destroy them from the inside. Just how this is done, for example, by the food germ, Listeria monocytogenes, has been studied by a team of scientists from the German Research Centre for Biotechnology (GBF) in Braunschweig and the University of Giessen. Their findings: the bacteria secrete a toxin that causes major alterations to the surface of host cells. These pathogens are then able to overcome the cell's defence mechanisms, making it easier for them to penetrate the cell. The results of the study have been published in the journal, Cellular Microbiology.
The primary boundary of life is defined by the cell membrane, an oily sheet made up of various fat molecules and proteins. In order to integrate and communicate important signals from the “outside world” into the cell, the proteins and fat molecules which make up the cell membrane have to work in a coordinated fashion. For that, some of the proteins and fat molecules are concentrated into viscous assemblies called "rafts". "These rafts," explains GBF work group leader, Dr. Siegfried Weiss, "are the key for many biochemical processes since they provide anchorage to many important regulatory molecules. Rafts are therefore in essence the ´trigger spots` where the cell processes signals received from the outside."
These key areas are the focus of Listeria monocytogenes. The bacteria produce a cell toxin that induces several small raft regions on the cell's surface to aggreagate together into a big, "super raft". "By this mechanism, the bacteria are able to activates the the rafts-associated regulatory molecules," says GBF junior scientist Nelson Gekara, "and these trigger different responses in the cell which for intance leads to a block in the cell´s defense mechanisms, much to the advantage of the invading bacteria." Furthermore, the rafts also function as a port-of-entry for the pathogens.
Listeria monocytogenes enters the human body from contaminated foodstuffs and can trigger intestinal ailments. People with weak immune systems are especially susceptible and therefore prone to the characteristic complications such as meningitis and abortion which stem from such infections.
"The mechanism with which Listeria attacks the surface of the targeted cell can tell us a lot about basic principles of infection," emphasizes Weiss. "We suspect that other, medically far more important pathogens proceed in a similar manner – for example, Streptococci or Bacillus anthracis, the anthrax pathogen." Weiss hopes that the Listeria cell toxin can help scientists better understand the function and importance of rafts on human cell surfaces.
More information can be found in the original article: Gekara, N., Jacobs, T., Chakraborty, T. and Weiss, S. "The cholesterol dependent cytolysin Listeriolysin O aggregates rafts via oligomerization".
A pre-publication online version of the article is available on the Web site of the journal Cellular Microbiology: www.blackwell-synergy.com/loi/ch
Photo material available at: www.gbf.de/presseinformationen
Gekara_Weiss_02.jpg: GBF work group leader Dr. Siegfried Weiss (left) with Nelson Gekara study the bacteria Listeriolysin O and its effect on human cells.
Listeria_MZ_01-03.jpg: View of rod-shaped cells of the bacteria, Listeria monocytogenes, attaching themselves to a human cell.
Photo: GBF/ Rohde
LLO and ERMp picture1-2.jpg: The impact of the bacteria toxin, Listeriolysin O (LLO), here in red, on the cell membrane. The protein, ERM, which plays an important role in transport processes inside the cell is shaded green in this coloration technique, but only when active. The fireworks of green signals illustrates that LLO is preparing the cell membrane for a transport process through the membrane, the prerequisite for bacteria to enter the cell.
Photo: GBF/Nelson Gekara