Essential proteins for malaria parasite survival discovered
MedWire News: Researchers have discovered a group of protein kinases that are essential for the survival of the malaria parasite in the human bloodstream.
"If we stop these proteins kinases from working then we kill the malaria parasites," commented study author Christian Doerig (Monash University, Victoria, Australia) in a press statement.
"We are now looking for drugs that do exactly that - stop the protein kinases from working. If we find these drugs then we will have a new way of killing the malaria parasite," he said.
Protein phosphorylation is a common regulatory mechanism that has been shown to be a useful drug target in many human diseases such as cancer. However, targeting this process in the malaria parasite has not been exploited, say the researchers, who add that this is largely due to a lack of information about the role of phosphorylation in Plasmodium falciparum biology.
As reported in the journal Nature Communications, the scientists combined two molecular techniques - global phosphoproteomic analysis and kinome-wide reverse genetics - to evaluate the role of protein phosphorylation in the asexual proliferation of P. Falciparum.
The phosphoproteomic analysis used mass spectroscopy to identify 1177 phosphorylation sites on 650 P. falciparum proteins that play a role in DNA synthesis, transcription, and metabolism, and in parasite invasion and cell adherence.
Using the kinome-wide reverse genetics strategy, the team discovered 36 P. falciparum protein kinases believed to be essential for successful asexual reproduction in the human bloodstream.
"The first thing you might want to do when considering targeting the parasite with new drugs is to consider which proteins you want your drug to work against," co-author Andrew Tobin (University of Leicester, UK) told MedWire News.
"Our study does just that - determines a group of proteins that are essential for the parasite. When we remove any one of these proteins, we kill the parasite," he added.
The investigators suggest that possible kinase inhibitors could be found by analyzing the results of recent screening programs carried out to identify chemicals with potential anti-malarial activity, as many of these chemicals have forms consistent with known protein kinase inhibitors.
"It seems perfectly realistic to us that we can now develop novel anti-malaria drugs based on the findings that we have made - it certainly is a big moment in our fight against this terrible disease that mainly affects the world's poorest people," said Tobin.
By Helen Albert