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Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.

ABSTRACT: The apicomplexan parasites that cause malaria and babesiosis invade and proliferate within erythrocytes. To assess the potential for common antiparasitic treatments, we measured the sensitivities of multiple species of Plasmodium and Babesia parasites to the chemically diverse collection of antimalarial compounds in the Malaria Box library. We observed that these parasites share sensitivities to a large fraction of the same inhibitors and we identified compounds with strong babesiacidal activity.

SUBMITTER: Paul AS

PROVIDER: S-EPMC4958166 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.

Paul Aditya S AS Moreira Cristina K CK Elsworth Brendan B Allred David R DR Duraisingh Manoj T MT

Antimicrobial agents and chemotherapy 20160722 8

The apicomplexan parasites that cause malaria and babesiosis invade and proliferate within erythrocytes. To assess the potential for common antiparasitic treatments, we measured the sensitivities of multiple species of Plasmodium and Babesia parasites to the chemically diverse collection of antimalarial compounds in the Malaria Box library. We observed that these parasites share sensitivities to a large fraction of the same inhibitors and we identified compounds with strong babesiacidal activity ...[more]

PMID: 27246780

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Project description:BackgroundMalaria is a one of the most important infectious diseases and is caused by parasitic protozoa of the genus Plasmodium. Previously, quantitative characterization of the P. falciparum transcriptome demonstrated that the strictly controlled progression of these parasites through their intra-erythrocytic developmental cycle is accompanied by a continuous cascade of gene expression. Although such analyses have proven immensely useful, the correlations between abundance of transcripts and their cognate proteins remain poorly characterized.ResultsHere, we present a quantitative time-course analysis of relative protein abundance for schizont-stage parasites (34 to 46 hours after invasion) based on two-dimensional differential gel electrophoresis of protein samples labeled with fluorescent dyes. For this purpose we analyzed parasite samples taken at 4-hour intervals from a tightly synchronized culture and established more than 500 individual protein abundance profiles with high temporal resolution and quantitative reproducibility. Approximately half of all profiles exhibit a significant change in abundance and 12% display an expression peak during the observed 12-hour time interval. Intriguingly, identification of 54 protein spots by mass spectrometry revealed that 58% of the corresponding proteins--including actin-I, enolase, eukaryotic initiation factor (eIF)4A, eIF5A, and several heat shock proteins--are represented by more than one isoform, presumably caused by post-translational modifications, with the various isoforms of a given protein frequently showing different expression patterns. Furthermore, comparisons with transcriptome data generated from the same parasite samples reveal evidence of significant post-transcriptional gene expression regulation.ConclusionsTogether, our data indicate that both post-transcriptional and post-translational events are widespread and of presumably great biological significance during the intra-erythrocytic development of P. falciparum.

Dataset Information

Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.

Publications

Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.

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