Unique protein is a vulnerability in the malaria parasite

Unique protein is a vulnerability in the malaria parasite

Over a thousand people die from malaria every day. The disease is caused by a single-cell parasite (protozoan) that is transmitted by mosquitoes. Anti-malaria efforts currently focus on effective diagnostics, mosquito nets, insecticides and drugs. Additionally, a strong effort is being is also made to develop a vaccine. Effective policy has nearly halved the annual number of malaria deaths in the past ten years, but further decline has stagnated, partly because the malaria parasite is developing resistance to all known drugs. Researchers discovered a protein in the mitochondrion of the malaria parasite that could be used as a target for such a new drug.

Almost all cells in the body contain mitochondria: organelles that provide energy to power cellular processes. The single-cell malaria parasite also has a mitochondrion, which is vital to its survival. All mitochondria contain many different proteins, including 'prohibitin' proteins. But malaria researchers discovered that the mitochondrion in the parasite, besides the common prohibitins that can also be found in human cells, contains a unique prohibitin that can be found only in this protozoa and related microbes.

This protein appears to be crucial for the survival of the parasite. Author said: "When we switched off the prohibitin in the parasite, we saw that it was no longer able to infect new mosquitoes. The prohibitin-free parasite was already struggling during the liver and blood stages of its life cycle, but the final blow was dealt when it tried to infect another mosquito: it failed to do so. Fertilization between male and female parasites in the mosquito midgut did occur, but shortly afterwards, this new generation died without infecting the mosquito."

Many mitochondrial functions depend on the voltage differential across the mitochondrial membrane. This membrane potential results from a difference in concentration of positively and negatively charged molecules inside and outside the mitochondrion. "The unique parasite protein fulfills an important role in maintaining the potential. In future research we want to figure out the exact mechanism." A new drug could potentially be developed to disable the unique prohibitin protein. "The main advantage is that this protein is not present in humans, who therefore cannot be harmed if it is disabled", author explains.

https://www.radboudumc.nl/en/news-items/2018/uniek-eiwit-vormt-zwakke-plek-malariaparasiet

http://www.cell.com/cell-reports/fulltext/S2211-1247(18)30449-2

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