Key Protein in the Spread of the Malaria Parasite Discovered

13/09/2018

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Gabriele Pradel

Cellular and Applied Infection Biology

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+49 241 80 20848

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An RWTH team has published research results.

In collaboration with her international partners, Professor Gabriele Pradel from the Chair of Cellular and Applied Infection Biology at the Institute for Biology II has been able to prove the existence of a protein that takes on a key role in the spread of the malaria parasite plasmodium falciparum.

Malaria causes approximately 400,000 deaths every year and is regarded as one of the most dangerous infectious diseases along with AIDS and tuberculosis. Responsible are unicellular parasites of the species plasmodium, which are transmitted to humans through the bite of mosquitoes. The virus first undergoes rapid asexual multiplication during the course of several life cycles, the cause of the high fever attacks of malaria infection typically experienced by the human hosts. After several such reproduction cycles, the parasite then begins to develop sexual forms in the infected host's blood called gametocytes, which remain sequestered within red blood cells until picked up into the midgut of female mosquitos during a blood meal. This initiates the next, sexual cycle of growth and multiplication of the parasite, representing a bottleneck factor in its life cycle. Within a time span of only 20 hours, the pathogens must leave their host cells, complete the fertilization process, and break through the intestinal eptithelium in order to escape the mosquito's hostile intestinal milieu.

This particular reprodutive stage of the parasite inside the midgut of the mosquito represents an ideal opportunity to mount intervention strategies and thereby keep at bay the malaria virus. Over the course of several years of research, the study has led to the identification and characterization of a protein that takes on a key function. It is the protein 7-Helix-1, which is specifically produced in female gametocytes. As the researchers have been able to show, 7-Helix-1 is a new type of regulator controlling the parasite's protein synthesis. A process that is increased markedly during fertilization, during which the parasite is preparing for the new milieu inside the midgut. Diverse moleculobiological and genetic methods have allowed researchers to identify several interactive partners of 7-Helix-1 that have already been recognized as factors in protein synthesis. Manufactured mutants, which were unable to create 7-Helix-1 anymore, were also not able to meet the increased demand for protein. The researchers were able to show that these mutants are characterized by changed gene expression that causes abnormal protein synthesis and thereby impairs parasite development.

If we can learn to successfully inhibit the function of 7-Helix-1 in plasmodium faciparum and thereby stop the parasite's sexual cycle of growth, the spread of malaria could be kept at bay and the number of associated deaths be reduced.

The results of the study have recently been published in the professional journal PLoS Pathogens.