MIT scientists have discovered a new drug target for treatment of the deadly malaria disease.
Researchers identified the drug target while studying the way in which the parasites Toxoplasma gondii, which causes toxoplasmosis, and Plasmodium, which causes malaria, access vital nutrients from their host cells.
Around one-third of the world's deadly infectious diseases, including malaria and tuberculosis, are caused by pathogens that spend a large portion of their life inside specially built compartments within their host cells.
These compartments, known as "parasitophorous vacuoles," separate the host cytoplasm and the parasite by a membrane, and thereby protect the parasites from the host cell's defenses.
They also provide an environment tailored to their needs, according to Dan Gold, who led the research in the laboratory of Jeroen Saeij, from the Massachusetts Institute of Technology (MIT)'s Department of Biology.
However, the membrane of these vacuoles also acts as a barrier between the parasite and the host cell.
This makes it more difficult for the parasite to release proteins involved in the transformation of the host cell beyond the membrane in order to spread the disease, and for the pathogen to gain access to vital nutrients, Gold said.
In Toxoplasma, the researchers discovered two proteins secreted by the parasite, known as GRA17 and GRA23, which are responsible for forming pores in the vacuole, Gold said.
They discovered the proteins' roles while investigating how the parasites are able to release their own protein into the host cell beyond the vacuole membrane after invasion.
Similar research into how the related Plasmodium pathogen performs this trick had identified a so-called "protein export complex" that transports encoded proteins from the parasite into its host red blood cell, which transforms these red blood cells in a way that is vital to the spread of malaria.
"The clinical symptoms of malaria are dependent on this process and this remodeling of the red blood cell that occurs," Gold said.
The researchers identified proteins secreted by Toxoplasma that appeared to be homologues, or of shared ancestry to this protein export complex in Plasmodium.
When they added dyes to the host cell, and knocked out the two proteins, the researchers found that it prevented the dyes flowing into the vacuole.
The researchers then expressed a Plasmodium export complex gene in the modified Toxoplasma and found that the dyes were able to flow into the vacuole once again, suggesting that this small-molecule transport function had been restored.
"All of this came together to strongly suggest that this protein that is involved in protein export in Plasmodium may also have an additional function in small-molecule transport," Gold said.
Since these proteins are only found in the parasite phylum Apicomplexa, to which both Toxoplasma and Plasmodium belong, they could be used as a drug target against the diseases they cause, including malaria, he said.
