In 2020, there were 241 million malaria cases and 627,000 deaths worldwide. The malaria parasite is transmitted to humans by the drab-looking female mosquito (Anopheles spp.) during their blood-sucking meals. Malaria can be treated with drugs, but the parasite is constantly evolving to evade death and build resistance to antimalarial treatments.
Now, scientists from the Australian National University (ANU) have discovered why malaria parasites are resistant to some drug therapies but vulnerable to others, which could lead to the development of effective antimalarial drugs. Their results are published in the journal PLOS Biology.
"We knew that parasites can be resistant to some drugs while simultaneously being susceptible to others, but we didn't know how this occurred," Said Dr Sarah Shafik, a co-author of the study, in a statement.
Two malaria proteins called PfMDR1 and PfCRT have been characterized by the research team. These proteins work together and transport drugs from areas that normally exert their killing effects to “safe zones”. This can render them ineffective, as some antimalarial treatments can only work when located in the stomach of the parasite.
This research used African clawed frog (Xenopus) immature eggs – or oocytes – to discover the function of the malaria protein. This may be an unusual organism to test this in, but it is often difficult to study these within the malaria parasite. There are many reasons for this: The first is the parasite is not viable outside the host cells; The second reason is when studying the function of a malaria parasite protein, it can sometimes be difficult to determine if the measured output is being influenced by other proteins in the parasite.
“It is often best to study the function of your protein of interest in a heterologous system such as the Xenopus oocyte system. Using this system, we can give the oocytes what they need to make our malaria protein of interest and once the protein is made, we can then directly measure the function of our protein of interest in isolation from confounding factors that are present in the parasite.” Shafik told IFLScience.
Along with being potentially involved in drug resistance, these proteins have also been found to be essential to the growth of the parasites. If these proteins are made inactive in future drugs, then there may be a good chance of eradicating malaria. The discovery may also help future cancer research, as there is a similar PfMDR1 protein that is also made by human cancer cells, so characterizing this protein may lead to future successful cancer treatments.
The future looks promising for this research, and there are many questions to now answer.
“Our lab is currently working on expanding this range of clinically relevant drugs, including those that are currently deployed in Africa and Southeast Asia, to ascertain if and how PfMDR1 and PfCRT are involved in the parasite’s acquisition of resistance to these drugs,” Shafik told IFLScience
“We’ve also recently been approached by other labs who are developing new drugs, asking us to test their new drugs against PfMDR1 and PfCRT in the Xenopus oocyte system so that we can give them information about how these new drugs might fare against these proteins.”
