Dataset Information

ATPase activity in Plasmodium falciparum asexual blood stages and gametocytes

ABSTRACT: Characterization of ATPase activity associated with gametocytogenesis in P. falciparum

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Plasmodium Falciparum

SUBMITTER: Matthew Monroe

LAB HEAD: Aaron Wright

PROVIDER: PXD005335 | Pride | 2017-10-31

REPOSITORIES: Pride

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Publications

A Global Survey of ATPase Activity in Plasmodium falciparum Asexual Blood Stages and Gametocytes.

Ortega Corrie C Frando Andrew A Webb-Robertson Bobbie-Jo BJ Anderson Lindsey N LN Fleck Neil N Flannery Erika L EL Fishbaugher Matthew M Murphree Taylor A TA Hansen Joshua R JR Smith Richard D RD Kappe Stefan H I SHI Wright Aaron T AT Grundner Christoph C

Molecular & cellular proteomics : MCP 20171027 1

Effective malaria control and elimination in hyperendemic areas of the world will require treatment of the Plasmodium falciparum (Pf) blood stage that causes disease as well as the gametocyte stage that is required for transmission from humans to the mosquito vector. Most currently used therapies do not kill gametocytes, a highly specialized, non-replicating sexual parasite stage. Further confounding next generation drug development against Pf is the unknown metabolic state ...[more]

PMID: 29079720

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Project description:For malaria transmission, the parasite must undergo sexual differentiation into mature gametocytes. However, the molecular basis for this critical transition in the parasites life cycle is unknown. Six previously uncharacterized genes, Pfg14.744, Pfg14.745, Pfg14.748, Pfg14.763, Pfg14.752 and Pfg6.6 that are members of a 36 gene Plasmodium falciparum-specific subtelomeric superfamily were found to be expressed in parasites that are committed to sexual development as suggested by co-expression of Pfs16 and Pfg27. Northern blots demonstrated that Pfg14.744 and Pfg14.748 were first expressed before the parasites differentiated into morphologically distinct gametocytes, transcription continued to increase until stage II gametocytes were formed and then rapidly decreased. Immunofluorescence assays indicated that both proteins were only produced in the subpopulation of ring stage parasites that are committed to gametocytogenesis and both localized to the parasitophorous vacuole (PV)b of the early ring stage parasites. As the parasites continued to develop Pfg14.748 remained within the parasitophorous vacuole, while Pfg14.744 was detected in the erythrocyte. The 5' flanking region of either gene alone was sufficient to drive early gametocyte specific expression of green fluorescent protein (GFP). In parasites transfected with a plasmid containing the Pfg14.748 5' flanking region immediately upstream of GFP, fluorescence was observed in a small number of schizonts the cycle before stage I gametocytes were observed. This expression pattern is consistent with commitment to sexual differentiation prior to merozoite release and erythrocyte invasion. Further investigation into the role of these genes in the transition from asexual to sexual differentiation could provide new strategies to block malaria transmission. Microarray analysis was used to compare two clones derived from Plasmodium falciparum strain 3D7 parasites that differ in their ability to undergo gametocytogenesis. Clone G+ produces gametocytes and clone G- produces very few if any gametocytes. RNA was harvested from the cultures when the asexual parasitemia was 0.9-1.48% (day 4) (n=4) after setting up the gametocyte cultures and 5.2-5.58% (day 6) (n=4) prior to the appearance of morphologically distinct gametocytes and used to generate cDNA that was labeled with Cy3 or Cy5 and hybridized to the Plasmodium falciparum 70 mer oligonucleotide microarray developed by DeRisi and co-workers.

Dataset Information

ATPase activity in Plasmodium falciparum asexual blood stages and gametocytes

Publications

A Global Survey of ATPase Activity in <i>Plasmodium falciparum</i> Asexual Blood Stages and Gametocytes.

Similar Datasets

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