doi:10.1038/nindia.2013.33 Published online 7 March 2013
The malaria parasite Plasmodium falciparum survives in the blood of humans by degrading hemoglobin into hemozoin. How the deadly parasite spins this trick has been an enigma for malaria researchers.
Scientists now say they have identified, for the first time, a protein complex responsible for this process1. The finding is expected to open doors for new antimalarials that act on this pathway.
"Formation of hemozoin from hemoglobin is essential for the malaria parasite's survival at asexual blood stages, but to date its underlying mechanisms were poorly understood," one of the authors Pawan Malhotra told Nature India.
In addition, a number of reports have suggested that this pathway is the target of two widely used antimalarials — chloroquine and artemisnin.
The researchers have shown that a protein complex containing several proteases and a heme detoxification protein is responsible for hemoglobin degradation and hemozoin formation in Plasmodium falciparum, the parasite that causes around 200 million cases of malaria worldwide.
They showed the association between these proteins experimentally by immunoprecipitation, mass spectrometry, co-elution/co-sedimentation and in vitro interaction analysis.
The researchers also developed an in vitro assay and elucidated the modes of action of chloroquine and artemisnin. They found that both these antimalarials acted during the heme polymerization step. Chloroqunie also acted at the hemoglobin degradation step.
"The in vitro assay will have important implications in screening of new antimalarials that act on this pathway," Malhotra added.
The authors of this work are from: International Centre for Genetic Engineering and Biotechnology and Hamdard University, New Delhi, India; and Seattle Biomedical Research Institute, Seattle, Washinton, USA.