Researchers have determined the reason why malaria parasites of the genus Plasmodium move ten times faster through the skin than immune cells,.
To find answer to that question, researchers studied actin, a protein that is important to the structure and movement of cells and that is built differently in parasites and mammals. The findings are not only changing our understanding of a key component of all living cells, but they also provide information that could help in the discovery of new drugs.
Actin is assembled into long rope-like structures called filaments. These filaments are important for the proper functioning of cells – such as muscle cells – and enable each of our movements. However, they also serve to enable immune system cells to move and capture invading pathogens. Likewise, they are of great importance for the movement of the malaria parasite. A key issue in the paper published in the journal PLOS Biology is how the rate at which actin filaments are formed and broken down differs between parasites and mammals.
It was known that certain sections of the actin protein differ between the parasite and mammals. To investigate the reasons behind the difference in speed, scientists replaced parts of the parasite protein with corresponding sections of protein from mammalian actin in the laboratory.
To investigate the underlying mechanism, the participating scientists performed experiments and computer simulations ranging from modeling at the molecular level to observing the parasites in live animals.
These findings could now be used to discover chemical compounds that selectively target parasite actin and affect either the building or breakdown of the filament.
An example for this approach is tubulin, another type of protein which is involved in the building of the cytoskeleton via so-called microtubules. Medicines that target parasite microtubules – such as mebendazole – have been successfully used for decades to treat humans and animals for parasitic worms. This joint research project was partially funded by the innovation fund FRONTIER at Heidelberg University.