Plasmodium falciparum is the pathogen responsible for the most devastating form of human malaria. As it replicates asexually in the erythrocytes of its human host, the parasite feeds on haemoglobin uptaken from these cells. Heme, a toxic by-product of haemoglobin utilization by the parasite, is neutralized into inert hemozoin in the food vacuole of the parasite. Lipid homeostasis and phospholipid metabolism are crucial for this process, as well as for the parasite’s survival and propagation within the host. P. falciparum harbours a uniquely large family of phospholipases, which are suggested to play key roles in lipid metabolism and utilization.
Mutaz Akkawi, Pascal Gisenya, Jérôme Munyangi, Pierre Lutgen
…or the key of malaria transmission.
Already 25 years ago it was known that malaria pigment (hemozoin, Hz, biocrystallized heme) is not an inert material. Crude pigment, as present in infected erythrocytes and shed after schizont rupture, may be considered the 'natural diet' ingested by macrophages in infected blood. Hemozoin is a powerful source of radicals, necrosis factor-alpha, interleukins 1 and 6.
Mutaz Akkawi, Jerome Munyangi, Pierre Lutgen
Already 200 years ago malaria pigment, later called hemozoin, was discovered.
Virchow, R. Zur pathologischen Physiologie des Bluts. Archiv f. pathol. Anat. 1, 547–563 (1847). https://doi.org/10.1007/BF02114475
Plasmodium parasites contain various virulence factors that modulate the host immune response. Malarial pigment, or hemozoin (Hz), is an undegradable crystalline product of the hemoglobin degradation pathway in the parasite and possesses immunomodulatory properties.
A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity.
The fight against tropical diseases such as malaria requires the development of innovative biosensing techniques. Diagnostics must be rapid and robust to ensure prompt case management and to avoid further transmission. The malaria biomarker hemozoin can catalyze atom transfer radical polymerizations (ATRP), which we exploit in a polymerization-amplified biosensing assay for hemozoin based on the precipitation polymerization of N-isopropyl acrylamide (NIPAAm).
Emergence of resistant Plasmodium species makes drug efficacy testing a crucial part of malaria control. Here we describe a novel assay for sensitive, fast and simple drug screening via the magneto-optical detection of hemozoin, a natural biomarker formed during the hemoglobin metabolism of Plasmodium species. By quantifying hemozoin production over the intraerythrocytic cycle, we reveal that hemozoin formation is already initiated by ~ 6-12 h old ring-stage parasites.
Here, we suggest an alternative optical methodology with an easy-to-use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study.