Researchers identify protein that evolved alongside infection mechanism

Toxoplasmosis is a worldwide infectious disease caused by the single-celled parasite Toxoplasma gondii. In humans, the infection poses a particular risk to pregnant women because it can lead to birth defects. Like the closely related malaria pathogen, Plasmodium falciparum, and other related species, T. gondii has special organelles, called rhoptries and micronemes, to infect the host cell.

A team led by Professor Markus Meissner, Chair of Experimental Parasitology at LMU, and Professor Joel Dacks from the University of Alberta (Canada) has now studied the evolution of this infectious machinery and identified a specific protein to organelles, which could become a promising target. for new therapeutic approaches. The article is published in Cell Reports.

During their evolution, parasites have not only developed particular organelles such as rhoptries and micronemes, but also all the protein machinery necessary to ensure the production and function of organelles.

The so-called organelle paralogy hypothesis (OPH) proposes that the current diversity of cellular organelles is due to the duplication and subsequent diversification over evolutionary time of certain genes that encode organelle identity.

“In order to create their specific structures, the parasites had to reuse certain proteins and add others,” explains Elena Jimenez-Ruiz, parasitologist at LMU.

Combination of bioinformatics and laboratory analyzes

To study the extent and manner in which organelle diversity emerged in the Apicomplexa, the group of organisms to which T. gondii and P. falciparum belong, the researchers combined comprehensive bioinformatics genetic analyzes and cell biology methods. molecular. In this way, the scientists were able to identify 18 candidate proteins that correlated with the emergence of new organelles and their protein machinery in apicomplexa.

“For one of these proteins, known as ArlX3, we were then able to demonstrate experimentally that it plays a key role in the formation of micronemes and rhoptries in T. gondii,” explains Jimenez-Ruiz. “Without ArlX3, parasites can no longer reproduce.”

Since ArlX3 is present in parasites but not in human cells, researchers believe the protein could represent a promising target structure for new therapeutic options. Additionally, their methods could potentially be used to identify other specific protein subgroups that could provide important insights into parasite cell biology.