Toxoplasmosis: a pathogen with a molecular master key

Parasitologists at LMU have demonstrated that a complex of two protein variants plays an important role
in Toxoplasma infection.

Toxoplasmosis is one of the most widespread zoonotic diseases worldwide and is an infectious disease
caused by the parasite Toxoplasma gondii.
Although cats are the last host, the parasite can infect any warm-blooded animal, including humans
.
In an investigation into how pathogens infect such a wide range of hosts, a team led by Professor Markus Meissner, LMU Chair in Experimental Parasitology
, identified a central protein complex.

Toxoplasma gondii belongs to the single-celled parasite phylum called the pointed composite phylum
.
In contrast to Toxoplasma gondii, most species in this group are limited to specific hosts and cell types
.
For example, the malaria pathogen Plasmodium is very species-specific and can only infect liver cells and red blood cells
.
The scientists believe that Toxoplasma gondii's wide host range suggests that the parasite can recognize multiple structures in host cells, thereby activating a central invasion complex
.

Dr Mirko Singh, lead author of the study, said: "Our hypothesis is that this invasion complex is highly conserved and present
in both Toxoplasma gondii and malaria parasites.
" "To investigate different host-specific invasion mechanisms and possible causes, we compared factors related to host invasion by Toxoplasma gondii and Plasmodium parasites
.
"

Interaction of the two variants

In their analysis of the invasion factors, the researchers focused on a huge family of cysteine repeat module proteins (CRMPs) that have been suspected of playing a role
in invasion.
Plasmodium has four of these proteins, while Toxoplasma gondii has only two
.
Through various experiments, the scientists succeeded in demonstrating that there are two variants of CRMP interacting in pairs – variant A interacts with variant B in each case
.
The entire complex assembles inside Toxoplasma gondii and then moves to the parasite's surface, where it begins to invade host cells
.
If one of the partners is removed, the parasite cannot penetrate its host cells – so the complex acts as the central "master key" to access the host
.

In addition, the scientists also found two other small helper proteins in Toxoplasma gondii, each specifically bound
to one of the variants.
"Without these helpers, it is more difficult for Toxoplasma gondii to invade cells, and interestingly, they are not present in the malaria parasite, which could explain the broader host range
of Toxoplasma gondii.
"