A team of MIT researchers has discovered a new target for drug treatments for prevalent diseases such as malaria. The findings focus on a membrane between the parasite and its host cell, with scientists successfully identifying a family of proteins that, when targeted, could cut off nutrients to the parasite.
Many diseases, such as malaria and tuberculosis, are caused by pathogens that exist in separate compartments within their host cells, known as parasitophorous vacuoles. The vacuole is separated from the host cytoplasm by a membrane, which protects the disease from the cell's defences. However, it also makes it difficult for the pathogen to access vital nutrients, and release the proteins necessary to spread the disease.
This means that the parasite has to develop a way to get around its own barrier in order to access nutrients essential to its survival. Previous studies have revealed that the membrane is selectively permeable, but scientists have been unable to determine the molecular makeup of the pores.
The MIT researchers were studying Toxoplasma, investigating how the parasite is able to release its proteins into the host cell and beyond, when they stumbled upon a discovery. They found that two proteins – GRA17 and GRA23 – were central to the process, and were of shared ancestry to proteins in the parasite Plasmodium, which were themselves responsible for a protein export system within their host cell.
However, when the team stopped the proteins from functioning, the export process of parasite proteins beyond the vacuole was unchanged. Puzzled by the specific role of the proteins in the export process, the researchers added dyes to the host cell and disabled the proteins once more.
Observing the cells again, they found that the proteins were no longer able to flow through the selective membrane and into the vacuole, strongly indicating that GRA17 and GRA23 are responsible for the small-molecule transfer between the host cell and the parasitophorous vacuole.
Furthermore, when the team switched the export protein from the Plasmodium parasite into the Toxoplasma, the dyes were able to flow into the vacuole once more, suggesting that the family of proteins responsible for the process had indeed been successfully identified.
"This very strongly suggests that you could find small-molecule drugs to target these pores, which would be very damaging to these parasites, but likely wouldn’t have any interaction with any human molecules," says research lead Dan Gold. "So I think this is a really strong potential drug target for restricting the access of these parasites to a set of nutrients."
The findings were recently published in journal Cell & Microbe.
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