Indian scientists find a way to disrupt parasite’s invasion of RBCs, open the door to beating drug-resistant strains
Indian scientists unlocking a way beat drug resistance in Plasmodium, the malarial parasite, is great news for the fight against the killer disease—of the 212 million cases in 2015, over 420,000 ended in death of the patient. Growing resistance to various anti-malarial treatments had sparked off alarm in the global medical community—parasite strains that are resistant to even the newest commercially available anti-malarial compound, artemisinin, are rapidly spreading in various geographies in South East Asia, a high-burden region. However, research by a team of scientists led by Anand Ranganathan of the Centre for Molecular Biology in JNU and Pawan Malhotra of the International Centre for Genetic Engineering and Biotechnology has indicated a potential mechanism to fight drug-resistant strains.
Part of the malaria parasite’s life-cycle within the human body occurs inside red-blood cells (RBCs). Given the parasite’s propensity to mutate—and thus develop resistance—Ranganathan et al focussed on understanding the pathway of infection of RBCs by the parasite. Cyclophilin B, an RBC surface-protein, acts as a receptor for the parasite ligand. The researchers found that preventing such binding via substitute biochemical ligands hobbles the parasite. They used cyclosporin A (an immunosuppressive medication) which binds to cyclophilin B, and observed a 80% reduction in Plasmodium invasion of RBCs. While cyclosporin-cyclophilin interactions have been studied since the late 1990s, this is the first time that cyclophilin’s role in malaria and the potential of using cyclosporin to check drug-resistant Plasmodium infection have been described. Plasmodium invasion of RBCs relies on two specific RBC receptors (one of which is cyclophilin) binding with the two specific proteins present on the parasite’s surface. Preventing any one of the linkages from forming would disrupt the infection. So, if cyclosporin action in this instance is found to be toxic for humans, the focus of future research can either be on bringing down its toxicity for humans or understanding the second linking mechanism and determining a method to interrupt that. Ranganathan et al may have just opened the door to beating malaria.