Scientists at the Helmholtz Zentrum fur Infektionsforschung (HZI), in Germany, have recently shed new light on an old mystery, related to the pathway used by the Listeria organism to invade the human body, causing listeriosis. The disease is a threat for people with compromised immune systems, as well as for the elderly and for children. In these patients, the condition can evolve very fast, and with fatal consequences. Experts have been puzzled over how it infects the body for a long time, but the new work appears to clear that out, paving the way for a new generation of potential treatments, AlphaGalileo reports.

Researchers weren't completely in the dark about how the pathogen infected the human body before the new study. They knew that, in the first stage, the organism would breach the intestinal barrier, and then enter the body. It then would activate a receptor molecule called “Met,” located on the surface of human cells. The way it accomplished this was by using the invasion protein known as internalin B. The signaling showed the cells that it needed to take Listeria in, essentially providing the organism with protection against the immune system. Details of the investigation appear in the November 6 issue of the respected scientific Journal of Molecular Biology.

The elusive research goal has been until now to determine the mechanisms that allowed the bacterial invasion protein to activate the human receptor. The HZI group was able to conclude that two molecules inside the protein were directly in charge of the activation process. Structural biologists at the Center first looked at the crystal structure of a single internalin B molecule, as well as at the complex that was binding to the human Met.

“In X-Ray structural analysis we noticed that in protein crystals two internalin B molecules align characteristically. This gave rise to the idea of a dimer – two congregated internalin B molecules – playing a pivotal role in the activation of the Met receptor,” University of Bielefeld Assistant Professor Hartmut Niemann, who has also been the head of the HZI structural biology team, explains. In order to confirm the hypothesis, researchers at the Center strengthened the correlation between the dimer components, and saw an increase in Listeria's uptake by human cells. A looser relationship saw the acceptance potential dropping considerably.