Abstract
Malaria transmission from an infected host to the mosquito vector requires the uptake of intraerythrocytic sexual precursor cells into the mosquito midgut. For the release of mature extracellular gametes two membrane barriers-the parasite parasitophorous vacuole membrane and the host red blood cell membrane-need to be dissolved. Membrane lysis occurs after the release of proteins from specialized secretory vesicles including osmiophilic bodies. In this study we conducted proteomic analyses of the P. berghei gametocyte egressome and developed a vesicular bioID approach to identify hitherto unknown proteins with a potential function in gametocyte egress. This first Plasmodium gametocyte egressome includes the proteins released by the parasite during the lysis of the parasitophorous vacuole membrane and red blood cell membrane. BioID of the osmiophilic body protein MDV1/PEG3 revealed a vesicular proteome of these gametocyte-specific secretory vesicles. Fluorescent protein tagging and gene deletion approaches were employed to validate and identify a set of novel factors essential for this lysis and egress process. Our study provides the first in vivo bioID for a rodent malaria parasite and together with the first Plasmodium gametocyte egressome identifies MTRAP as a novel factor essential for mosquito transmission. Our data provide an important resource for proteins potentially involved in a key step of gametogenesis.
Highlights
Malaria caused 214 million clinical cases in 2015 [1]
MDV1/PEG3, GEST, and G377 localize to osmiophilic bodies (OB), PPLP2 has been suggested to inhabit a separate population of egress vesicles
Male ⌬gest microgametes show aberrant exflagellation [7]. ⌬mdv1/peg3 parasites in contrast have no or few OB and are defect in parasitophorous vacuole membrane (PVM) and RBC rupture, which leads to low transmission into mosquitoes [8]. ⌬g377 parasites have a reduced number of OB but no defect in MDV1/PEG3 packaging [9]; microgametes still exflagellate like wildtype but egress of females is significantly reduced, which results in reduced transmission to the mosquito [10]
Summary
Malaria caused 214 million clinical cases in 2015 [1]. The infection is initiated when the mosquito injects sporozoites from its salivary glands into the skin during a bite. Tagging of OB Protein MDV1/PEG3 with BirA*—In order to identify which proteins are present in osmiophilic bodies we adapted the BioID methodology [15] for the use of in vivo labeling of proteins of P. berghei gametocytes present in circulating red blood cells of the mouse host.
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