Scientists have uncovered a potential mode of parasite drug resistance in malaria infection. Transmitted via a mosquito bite, the parasite Plasmodium enters the bloodstream and infects red blood cells. The parasite then digests hemoglobin the oxygen carrying protein in the blood and converts it into hemozoin, a protein indispensable for parasite survival.
While some of the current anti-malarial drugs target this digestion pathway, resistance to these drugs has also been reported and to address this resistance, Leiden University Medical Centre researcher Shahid Khan and colleagues created a mouse parasite lacking critical "Pac-Man" enzymes required to chew up hemoglobin.
These mutant parasites are able to survive and multiply inside immature red blood cells called reticulocytes, without making hemozoin. Surprisingly, the mutant parasites cannot be killed by the anti-malarial drug chloroquine, which interferes with hemozoin formation, but yet, remain sensitive to the drug artesunate which targets another pathway of hemoglobin digestion.
The finding that hemozoin formation is not essential for parasite survival in reticulocytes suggests that the parasites can develop different means of survival in the blood affording them certain drug resistance. These discoveries may help guide future research targeting human malaria parasites that can only grow inside reticulocytes and opens up new opportunities for the design of anti-malarial drugs to treat refractory patients.
The study is published in The Journal of Experimental Medicine