31 Oct 2025
Researchers at LMU and the Bernhard Nocht Institute for Tropical Medicine (BNITM) have elucidated how the pathogens build and organize their cell structures and transport systems in order to survive.
Malaria and toxoplasmosis are two of the most common infectious diseases in the world. Although there are drugs against malaria and toxoplasmosis, they do not work for all stages of the disease, they can have side effects, and they are partially losing their effectiveness through drug resistance. New pharmaceutical agents are needed to target the pathogens and kill them for good. A better understanding of cell biological processes is crucial for developing new approaches for therapies and vaccines.
Malaria and toxoplasmosis are caused by apicomplexan parasites. These are single-celled pathogens which can only propagate inside host cells. Malaria occurs when parasites of the genus Plasmodium enter the human bloodstream through the sting of infected Anopheles mosquitoes. These infections cause high fever, chills, and, in serious cases, life-threatening organ damage. According to the World Health Organization, around 240 million people contract malaria every year. More than 600,000 of these die from the disease, especially children in Sub-Saharan Africa. Toxoplasmosis, which is triggered by the parasite Toxoplasma gondii, affects around a third of the population worldwide. The infection usually passes unnoticed, but it can cause severe complications in pregnant women and the immunocompromised.
Research findings which have recently been published in the Journal of Cell Biology and PLOS Biology could pave the way for new treatment methods to combat these two widespread infectious diseases.
Markus Meißner is Chair Professor of Experimental Parasitology at LMU. He and his team identified a new transport pathway in the parasite Toxoplasma gondii by investigating a parasite gene that was previously little understood. This gene encodes the protein tepsin, which cooperates closely with the adaptor protein AP-4 and ensures that little bubbles, so-called vesicles, within the parasite get to their destination. Interestingly, the researchers found that the structural protein clathrin also plays a role here. In animals, this mechanism works differently, as the adaptor complex AP-4 works without clathrin. Plants, by contrast, actively use clathrin to form vesicles. It is precisely this mechanism that Toxoplasma gondii uses.
As revealed by a study from the laboratory of Dr. Tobias Spielmann, leader of the Malaria Cell Biology research group at BNITM, this mechanism is also present in malaria parasites. This discovery suggests that Toxoplasma gondii and malaria parasites developed a highly specialized yet conserved transport system in the course of evolution: “Our results show that these parasites conserved a very ancient transport mechanism, which is adapted to their unique biology,” explains Meißner.
Furthermore, the research group led by Dr. Simon Gras at LMU Munich discovered that Toxoplasma constantly recycles parts of its plasma membrane during growth and division. “We were astonished how dynamic this process is,” says Gras. “It’s a brilliant example of how evolution repurposes old cellular tricks to solve new challenges.”
Dr. Tobias Spielmann’s team at BNITM joined forces with the Integrative Parasitology research group led by Dr. Richárd Bártfai at Radboud University to investigate the protein complexes AP-1, AP-3, and AP-4 (adaptor proteins). They discovered that AP-1, AP-3, and AP-4 play a decisive role in the survival of the malaria parasite.
Before the researchers tackled this problem, it was little understood how proteins are distributed in the malaria parasite. As their findings reveal, the adaptors ensure that proteins reach the right place in the cell. In the malaria pathogen, this transport process is particularly important, as it is required both for penetration into host cells and for growth inside the cells.
The structure of these transport mechanisms in malaria parasites bears a remarkable resemblance to those of other living creatures, even though the organisms have diverged strongly over the course of evolution. At the same time, the system has some unusual characteristics that were previously unknown. “Using state-of-the-art imaging and protein analyses, we established that these adaptor systems function like logistics centers and share a surprisingly large number of commonalities with similar processes in human cells,” says Spielmann.
The findings of the research groups from Hamburg and Munich open up new perspectives on the fundamental cell biology of apicomplexan parasites, which include the malaria and toxoplasmosis parasites. The studies highlight both common and unique biological features of different species. In the long term, they could help researchers identify new points of attack for therapies against malaria and toxoplasmosis.
Publications:
Janessa Grech et al.: Tepsin and AP4 mediate transport from the trans-Golgi to the plant-like vacuole in toxoplasma. Journal of Cell Biology 2025
Julia von Knoerzer-Suckow et al.: Plasma membrane recycling drives reservoir formation during Toxoplasma gondii intracellular replication. PLOS Biology 2025
José Cubillán-Marín et al.: Vesicle adaptors in malaria parasites show conservation and flexibility of protein sorting machinery. Journal of Cell Biology 2025