Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)

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Parasite Lifecycle Stages
Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)

Stage ID:	5
Name:	Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
Associated with:	8 targets
	17 ligands

Description
Any lifecycle stage of Plasmodium that is spent in the invertebrate vector (female Anopheles mosquitos) and can include: gametocyte, the sexually committed form of the parasite that is ingested by the vector during a blood meal. The process of ingestion induces the production of gametes and release from the host erythrocyte into the mosquito midgut. gamete, the male gametocyte divides to give many flagellated microgametes, whereas the female gametocyte differentiates to a macrogamete. zygote, diploid stage formed by fusion of a male and female gamete. Meiosis occurs in the zygote which then develops into the ookinete. ookinete, the motile form of the parasite that develops from the zygote. The ookinete penetrates through the epithelial cells lining the midgut of the mosquito where it differentiates into an oocyst. oocyst, a thick-walled structure that forms under the mosquito's outer gut lining. The oocyst undergos asexual replication, called sporogony, which culminates in the production of several thousand sporozoites. Upon maturation the oocyst ruptures and releases the sporozoites into the hemocoel of the mosquito. sporozoite, a motile form of the parasite that is responsible for the initial infection of the host. Following release from the oocyst, sporozoites migrate to the salivary glands of the vector with a few injected into the host during the mosquito's blood meal. Blocking development of the parasite during this stage prevents transmission from mosquito to human.

Description

Any lifecycle stage of Plasmodium that is spent in the invertebrate vector (female Anopheles mosquitos) and can include:

gametocyte, the sexually committed form of the parasite that is ingested by the vector during a blood meal. The process of ingestion induces the production of gametes and release from the host erythrocyte into the mosquito midgut.
gamete, the male gametocyte divides to give many flagellated microgametes, whereas the female gametocyte differentiates to a macrogamete.
zygote, diploid stage formed by fusion of a male and female gamete. Meiosis occurs in the zygote which then develops into the ookinete.
ookinete, the motile form of the parasite that develops from the zygote. The ookinete penetrates through the epithelial cells lining the midgut of the mosquito where it differentiates into an oocyst.
oocyst, a thick-walled structure that forms under the mosquito's outer gut lining. The oocyst undergos asexual replication, called sporogony, which culminates in the production of several thousand sporozoites. Upon maturation the oocyst ruptures and releases the sporozoites into the hemocoel of the mosquito.
sporozoite, a motile form of the parasite that is responsible for the initial infection of the host. Following release from the oocyst, sporozoites migrate to the salivary glands of the vector with a few injected into the host during the mosquito's blood meal.

Blocking development of the parasite during this stage prevents transmission from mosquito to human.

Interactions

Key to terms and symbols

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Target	Ligand		Sp.	Action	Value	Parameter	Reference
Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase	cipargamin		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	-	-	14
	cipargamin	Oocyst count: significantly reduced count observed with the addition of cipargamin when compared to control feeds [14] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum non-SERCA-type Ca2+ -transporting P-ATPase	compound 1a [WO2021204952A1]		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	-	-	6
	compound 1a [WO2021204952A1]	Relative oocyst intensities, determined using transgenic reporter strain P. falciparum NF54-HGL, show that compound 1a has transmission-blocking potential [6] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum phosphatidylinositol 4-kinase beta	MMV048		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	6.9	pIC₅₀	11
Plasmodium falciparum phosphatidylinositol 4-kinase beta	MMV048	pIC₅₀ 6.9 (IC₅₀ 1.11x10^-7 M) Indirect SMFA [11] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	7.0 – 7.1	pIC₅₀	3
Plasmodium falciparum phosphatidylinositol 4-kinase beta	UCT943	pIC₅₀ 7.1 (IC₅₀ 8x10^-8 M) Reports on the functional viability of male and female mature stage V gametocytes [3] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite dual gamete formation assay (DGFA) pIC₅₀ 7.0 (IC₅₀ 9.6x10^-8 M) [3] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum elongation factor 2	M5717		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	8.0 – 8.9	pEC₅₀	2
Plasmodium falciparum elongation factor 2	M5717	pEC₅₀ 8.9 (EC₅₀ 1.2x10^-9 M) Female gamete formation [2] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite gamete formation assay pEC₅₀ 8.7 (EC₅₀ 1.8x10^-9 M) Indirect SMFA [2] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA) pEC₅₀ 8.7 (EC₅₀ 1.8x10^-9 M) Male gamete formation [2] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite gamete formation assay pEC₅₀ 8.0 (EC₅₀ 1x10^-8 M) Direct SMFA [2] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase	P218		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	8.4	pIC₅₀	12
	P218	pIC₅₀ 8.4 (IC₅₀ 4x10^-9 M) Induction of male gamete activation (exflagellation) following 48 hour exposure of mature gametocytes to P218 [12] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite exflagellation assay
Plasmodium falciparum cGMP-dependent protein kinase	MMV030084		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	6.8	pIC₅₀	15
Plasmodium falciparum cGMP-dependent protein kinase	MMV030084	pIC₅₀ 6.8 (IC₅₀ 1.41x10^-7 M) Dual Gamete Formation Assay (DGFA): male gamete exflagellation was inhibited in the presence of MMV030084, but not when the compound was washed out prior to gamete formation. Activity against female gametes was not clearly identified [15] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite exflagellation assay
Plasmodium falciparum lysyl-tRNA synthetase	compound 5 [PMID: 30894487]		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	<6.0	pEC₅₀	1
Plasmodium falciparum lysyl-tRNA synthetase	compound 5 [PMID: 30894487]	pEC₅₀ <6.0 (EC₅₀ >1x10^-6 M) [1] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite gamete formation assay
Plasmodium falciparum plasmepsin X	WM382		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	-	-	5
Plasmodium falciparum plasmepsin X	WM382	Oocyst count: potent inhibition of oocyst development [5] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Plasmodium falciparum plasmepsin V	WEHI-842		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	-	-	7
Plasmodium falciparum plasmepsin V	WEHI-842	Oocyst count: WEHI-842 demonstrates a dose-dependent inhibitory effect on transmission fitness [7] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Unknown MOA	SQ-109		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	-	-	13
Unknown MOA	SQ-109	≥80% inhibition of male gamete exflagellation following 48hour exposure of mature gametocytes to 2µM SQ-109 [13] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite exflagellation assay
Unknown MOA	OSM-S-38		Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	8.4	pIC₅₀	16
Unknown MOA	OSM-S-38	pIC₅₀ 8.4 (IC₅₀ 4x10^-9 M) [16] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite late stage (IV–V) gametocyte assay
Unknown MOA	ganaplacide		PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖	-	-	-	8
Unknown MOA	ganaplacide	Oocyst count: >90% reduction of oocyst numbers at a concentration of 500 nM [8] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Unknown MOA	artefenomel		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	-	-	4
Unknown MOA	artefenomel	>60% inhibition of exflagellation following 24hour exposure of mature gametocytes to 10µM artefenomel [4] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite exflagellation assay
Unknown MOA	ACT-451840		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	7.5	pIC₅₀	9
Unknown MOA	ACT-451840	pIC₅₀ 7.5 (IC₅₀ 3x10^-8 M) Indirect mode: dose-dependent inhibition of oocyst development in the mosquito was observed. Direct mode: no activity at concentrations up to 1 μM [9] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)
Unknown MOA	GSK369796		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	-	-	4
Unknown MOA	GSK369796	Total inhibition of exflagellation following 24hour exposure of mature gametocytes to 10µM GSK369796 [4] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Parasite exflagellation assay
Unknown MOA	E209		Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖	-	7.8	pIC₅₀	10
Unknown MOA	E209	pIC₅₀ 7.8 (IC₅₀ 1.45x10^-8 M) determined by the reduction in oocyst mean intensity. A corresponding ~60 and 90% transmission blocking activity (defined as the percentage of mosquitoes with no observed oocysts) was determined at 100nM and 1µM, respectively [10] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Description: Standard membrane feeding assay (SMFA)

References

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