The logistics of parasites

Scientists from the Bernhard Nocht Institute for Tropical Medicine (BNITM) and the Ludwig Maximilian University of Munich (LMU) have discovered how malaria and toxoplasmosis pathogens build and organise their cell structures and transport systems in order to survive. Their discoveries could pave the way for new treatments against these globally significant infectious diseases. The research results were recently published in the Journal of Cell Biology and PLOS Biology.

At the BNITM, the team led by Dr Tobias Spielmann, head of the Malaria Cell Biology working group, together with Dr Richárd Bártfai’s research group Integrative Parasitology from Radboud University Nijmegen, examined the protein complexes AP-1, AP-3 and AP-4 (adapter proteins). They discovered that AP-1, AP-3 and AP-4 play a crucial role in the survival of the malaria parasite. Until now, little was known about how proteins are distributed within the malaria parasite. The researchers have now shown that the adapters ensure that proteins reach their right location within the cell. This transport process is particularly important for the malaria pathogen, as it is necessary both for host cell invasion and intracellular growth.

How parasites reuse ancient cell mechanisms

Remarkably, the structure of these transport mechanisms in malaria parasites is similar to that of other organisms, even though the organisms have diverged greatly from each other in the course of evolution. At the same time, the system also has unusual features that were previously unknown. "Using cutting-edge imaging and protein analysis, we have found that these adapter systems work much like logistics hubs and even share features with similar processes in human cells," says Spielmann.

Prof. Markus Meißner, head of the Department of Experimental Parasitology at LMU, and his team identified a new transport pathway in the parasite Toxoplasma gondii. They investigated a parasite gene that was previously poorly understood. It encodes the protein tepsin, which works closely with the adapter protein AP-4 to ensure that small vesicles within the parasite reach their destination. Interestingly, the structural protein clathrin also plays a role in this process. This mechanism works differently in animals, where the AP-4 adapter complex functions without clathrin. Plants, on the other hand, actively use clathrin to form vesicles. Toxoplasma gondii uses precisely this mechanism. As the study from the Spielmann laboratory shows, this mechanism is also found in the malaria parasite. This discovery shows that Toxoplasma gondii and malaria parasites have developed a highly specialised yet conserved transport system in the course of evolution:  "Our results show that these parasites have retained a very ancient transport mechanism that has been adapted to their unique biology," explains Meißner.

In addition, Dr Simon Gras’s group at LMU discovered that Toxoplasma constantly recycles parts of its outer membrane during as it grows and divides. "We were amazed at how dynamic this process is," says Gras. “It is a brilliant example of how evolution reuses old cellular tricks to solve new challenges.”

Thinking about new therapies

The findings of the research groups from Hamburg and Munich open up new perspectives on the fundamental cell biology of apicomplexan parasites, which include malaria and toxoplasmosis parasites. The work highlights both shared and unique biological characteristics of different species and could contribute in the long term to finding new targets for therapies against malaria and toxoplasmosis.

Two diseases of global significance

Malaria and toxoplasmosis are among the most significant infectious diseases worldwide. Although there are drugs available to treat malaria and toxoplasmosis, they are not effective in all stages of the disease, can have side effects and, in some cases, lose their effectiveness due to resistance. New active substances are needed to combat the pathogens permanently and specifically. Gaining a better understanding of cellular processes is key to identifying new targets for therapies and vaccines.

Malaria and toxoplasmosis are caused by apicomplexan parasites. These are single-celled pathogens that can only reproduce within host cells. Malaria develops when parasites of the genus Plasmodium enter the human bloodstream through the bite of infected Anopheles mosquitoes. They cause high fever, chills and, in severe cases, life-threatening organ damage. According to the WHO, more than 240 million people contract malaria every year. More than 600,000 die as a result, mainly children in sub-Saharan Africa. Toxoplasmosis, caused by the parasite Toxoplasma gondii, affects around one third of the world's population. The infection usually goes unnoticed, but can cause serious complications in pregnant women and immunocompromised individuals. 

Publications

Cubillán-Marín J et al., Vesicle adapters in malaria parasites show conservation and flexibility of protein sorting machinery, Journal of Cell Biology 2025, doi: 10.1083/jcb.202504062

Grech J et al., Tepsin and AP4 mediate transport from the trans-Golgi to the plant-like vacuole in toxoplasma, Journal of Cell Biology 2025, doi: 10.1083/jcb.202312109

Von Knoerzer-Suckow J et al., Plasma membrane recycling drives reservoir formation during Toxoplasma gondii intracellular replication, PLOS Biology 2025, doi: 10.1371/journal.pbio.3003415

More information and contact

Press release – Bernhard Nocht Institute for Tropical Medicine (BNITM)