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ATPase activity in Plasmodium falciparum asexual blood stages and gametocytes

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

INSTRUMENT(S):

ORGANISM(S): Plasmodium Falciparum

SUBMITTER: Matthew Monroe

LAB HEAD: Aaron Wright

PROVIDER: PXD005335 | Pride | 2017-10-31

REPOSITORIES: Pride

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			Action	DRS
	SBRI_Pfalci_ASschizont_ATP_1_1May15_Falcon_15-02-03.mgf	Mgf
	SBRI_Pfalci_ASschizont_ATP_1_1May15_Falcon_15-02-03.pride.mgf.gz	Mgf
	SBRI_Pfalci_ASschizont_ATP_1_1May15_Falcon_15-02-03.raw	Raw
	SBRI_Pfalci_ASschizont_ATP_1_1May15_Falcon_15-02-03_msgfplus.mzid.gz	Mzid
	SBRI_Pfalci_ASschizont_ATP_1_1May15_Falcon_15-02-03_msgfplus.pride.mztab.gz	Mztab

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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

Similar Datasets

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

Project description: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 of the gametocyte and the lack of known biochemical activity for most parasite gene products in general. Here, we take a systematic activity-based proteomics approach to survey the activity of the large and druggable ATPase family in replicating blood stage asexual parasites and transmissible, non-replicating sexual gametocytes. ATPase activity broadly changes during the transition from asexual schizonts to sexual gametocytes, indicating altered metabolism and regulatory roles of ATPases specific for each lifecycle stage. We further experimentally confirm existing annotation and predict ATPase function for 38 uncharacterized proteins. By mapping the activity of ATPases associated with gametocytogenesis, we assign biochemical activity to a large number of uncharacterized proteins and identify new candidate transmission blocking targets.

| S-EPMC5750841 | biostudies-literature

In Vitro Activities of Primaquine-Schizonticide Combinations on Asexual Blood Stages and Gametocytes of Plasmodium falciparum.

Project description:Currently, the World Health Organization recommends addition of a 0.25-mg base/kg single dose of primaquine (PQ) to artemisinin combination therapies (ACTs) for Plasmodium falciparum malaria as a gametocytocidal agent for reducing transmission. Here, we investigated the potential interactions of PQ with the long-lasting components of the ACT drugs for eliminating the asexual blood stages and gametocytes of in vitro-cultured P. falciparum strains. Using the SYBR green I assay for asexual parasites and a flow cytometry-based assay for gametocytes, we determined the interactions of PQ with the schizonticides chloroquine, mefloquine, piperaquine, lumefantrine, and naphthoquine. With the sums of fractional inhibitory concentrations and isobolograms, we were able to determine mostly synergistic interactions for the various PQ and schizonticide combinations on the blood stages of P. falciparum laboratory strains. The synergism in inhibiting asexual stages and gametocytes was highly evident with PQ-naphthoquine, whereas synergism was moderate for the PQ-piperaquine, PQ-chloroquine, and PQ-mefloquine combinations. We have detected potentially antagonistic interactions between PQ and lumefantrine under certain drug combination ratios, suggesting that precautions might be needed when PQ is added as the gametocytocide to the artemether-lumefantrine ACT (Coartem).

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Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages

Project description:Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages

2017-08-21 | GSE102167 | GEO

Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S-transferases

Project description:Characterization of Glutathione S-transferase activity associated with phase II drug metabolism.

2018-10-22 | PXD006920 | Pride

Transcriptome analysis of immature and mature male and female gametocytes of the malaria parasite Plasmodium falciparum

Project description:In the human host, Plasmodium falciparum parasites propagate asexually in erythrocytes causing the symptoms of malaria. However, in every asexual cycle, a small proportion of the parasites commits to sexual differentiation, which is critical for transmission. During a period of about 10 days, the sexually committed parasites either develop into male or female gametocytes. In this study, gametocytes carrying an endogenously GFP tagged version of the female specifically expressed ABCG2 gene were FACS sorted to separate male (GFP low) and female (GFP high) gametocyte populations at different days of development. RNA was subsequently extracted from these populations as well as from asexual parasites as controls and subjected to directional RNAseq. These data reveal the transcriptional differences between asexual parasite stages and developing gametocytes, but also between male and female gametocytes as well as for each sex during the course of differentiation. In particular, male gametocytes undergo distinct transcriptional transitions when comparing the transcriptome between day 4, 6 and 10 of gametocytogenesis. In contrast, female gametocyte transcriptomes are more static during the course of gametocytogenesis and only show minimal variation. This is the first study to longitudinally monitor gene expression in developing male and female gametocytes

2021-07-31 | GSE180985 | GEO

Activity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood Stages.

Project description:Earlier genetic and inhibitor studies showed that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new antimalarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum We observed ≥90% inhibition at 10 μM for 28% of compounds against asexual blood stages and early gametocytes, of which a third retained ≥90% inhibition at 1 μM.

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Small RNA sequencing in asexual stages of Plasmodium falciparum NF54

Project description:To investigate the accumulation of non coding small RNAs we performed high throughput RNA sequencing on size selcted total RNA from malaria parasite Plasmodium falciparum

2018-08-22 | GSE107625 | GEO

Activity-based protein profiling of the mouse gut microbiome in response to high or low fiber diets

Project description:Gastrointestinal content of mice fed high or low fiber diets was labeled with the GH2c-ABP. 3x replicates of each diet, 2x littermates per diet. 12 total mice.

2022-08-11 | PXD018644 | Pride

Genome-wide regulatory dynamics of translation in the Plasmodium falciparum asexual blood stages.

Project description:The characterization of the transcriptome and proteome of Plasmodium falciparum has been a tremendous resource for the understanding of the molecular physiology of this parasite. However, the translational dynamics that link steady-state mRNA with protein levels are not well understood. In this study, we bridge this disconnect by measuring genome-wide translation using ribosome profiling, through five stages of the P. falciparum blood phase developmental cycle. Our findings show that transcription and translation are tightly coupled, with overt translational control occurring for less than 10% of the transcriptome. Translationally regulated genes are predominantly associated with merozoite egress functions. We systematically define mRNA 5' leader sequences, and 3' UTRs, as well as antisense transcripts, along with ribosome occupancy for each, and establish that accumulation of ribosomes on 5' leaders is a common transcript feature. This work represents the highest resolution and broadest portrait of gene expression and translation to date for this medically important parasite.

| S-EPMC4371882 | biostudies-literature

Widespread occurrence of lysine methylation in Plasmodium falciparum proteins at asexual blood stages.

Project description:Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites. Using liquid chromatography and tandem mass spectrometry analysis, 570 lysine methylated proteins at three different blood stages were identified. Analysis of the peptide sequences identified 605 methylated sites within 422 proteins. Functional classification of the methylated proteins revealed that the proteins are mainly involved in nucleotide metabolic processes, chromatin organization, transport, homeostatic processes and protein folding. The motif analysis of the methylated lysine peptides reveals novel motifs. Many of the identified lysine methylated proteins are also interacting partners/substrates of PfSET domain proteins as revealed by STRING database analysis. Our findings suggest that the protein methylation at lysine residues is widespread in Plasmodium and plays an important regulatory role in diverse set of the parasite pathways.

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