Abstract
An essential step in the transmission of the malaria parasite to the Anopheles vector is the transformation of the mature gametocytes into gametes in the mosquito gut, where they egress from the erythrocytes and mate to produce a zygote, which matures into a motile ookinete. Osmiophilic bodies are electron dense secretory organelles of the female gametocytes which discharge their contents during gamete formation, suggestive of a role in gamete egress. Only one protein with no functional annotation, Pfg377, is described to specifically reside in osmiophilic bodies in Plasmodium falciparum Importantly, Pfg377 defective gametocytes lack osmiophilic bodies and fail to infect mosquitoes, as confirmed here with newly produced pfg377 disrupted parasites. The unique feature of Pfg377 defective gametocytes of lacking osmiophilic bodies was here exploited to perform comparative, label free, global and affinity proteomics analyses of mutant and wild type gametocytes to identify components of these organelles. Subcellular localization studies with fluorescent reporter gene fusions and specific antibodies revealed an osmiophilic body localization for four out of five candidate gene products analyzed: the proteases PfSUB2 (subtilisin 2) and PfDPAP2 (Dipeptidyl aminopeptidase 2), the ortholog of the osmiophilic body component of the rodent malaria gametocytes PbGEST and a previously nonannotated 13 kDa protein. These results establish that osmiophilic bodies and their components are dispensable or marginally contribute (PfDPAP2) to gamete egress. Instead, this work reveals a previously unsuspected role of these organelles in P. falciparum development in the mosquito vector.
Highlights
Each year more than 200 million people suffer from malaria, with an estimated death toll of 438.000 in 2015 [1]
An essential step in the transmission of the malaria parasite to the Anopheles vector is the transformation of the mature gametocytes into gametes in the mosquito gut, where they egress from the erythrocytes and mate to produce a zygote, which matures into a motile ookinete
Osmiophilic bodies are electron dense secretory organelles of the female gametocytes which discharge their contents during gamete formation, suggestive of a role in gamete egress
Summary
Each year more than 200 million people suffer from malaria, with an estimated death toll of 438.000 in 2015 [1]. Malaria infection in humans is initiated by the bite of an infected Anopheles mosquito, which inoculates hundreds of sporozoites that migrate into the blood stream to reach the liver hepatocytes. Blood stage asexual parasites undergo indefinite cycles of merozoite proliferation, egress from the host cell and reinvasion of new RBCs, causing malaria symptoms. A fraction of parasites enter sexual differentiation (gametocytogenesis). This process takes place in the bone marrow where the parasites go through five morphologically distinct stages, culminating after 10 days in the formation of the falciform mature gametocytes. The zygote transforms into an ookinete, which traverses the mosquito midgut epithelium to develop into an oocyst, producing several thousand sporozoites able to migrate to the mosquito salivary glands, ready to infect a new human host [3]
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