Inducible developmental reprogramming redefines commitment to sexual development by malaria parasites

Kent, R. S., Modrzynska, K. K. , Cameron, R., Philip, N., Billker, O. and Waters, A. P. (2018) Inducible developmental reprogramming redefines commitment to sexual development by malaria parasites. Nature Microbiology, 3(11), pp. 1206-1213. (doi:10.1038/s41564-018-0223-6) (PMID:30177743) (PMCID:PMC6317699)

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Abstract

During malaria infection, Plasmodium spp. parasites cyclically invade red blood cells and can follow two different developmental pathways. They can either replicate asexually to sustain the infection, or differentiate into gametocytes, the sexual stage that can be taken up by mosquitoes, ultimately leading to disease transmission. Despite its importance for malaria control, the process of gametocytogenesis remains poorly understood, partially due to the difficulty of generating high numbers of sexually committed parasites in laboratory conditions1. Recently, an apicomplexa-specific transcription factor (AP2-G) was identified as necessary for gametocyte production in multiple Plasmodium species2,3, and suggested to be an epigenetically regulated master switch that initiates gametocytogenesis4,5. Here we show that in a rodent malaria parasite, Plasmodium berghei, conditional overexpression of AP2-G can be used to synchronously convert the great majority of the population into fertile gametocytes. This discovery allowed us to redefine the time frame of sexual commitment, identify a number of putative AP2-G targets and chart the sequence of transcriptional changes through gametocyte development, including the observation that gender-specific transcription occurred within 6 h of induction. These data provide entry points for further detailed characterization of the key process required for malaria transmission.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cameron, Mrs Rachael and Kent, Miss Robyn and Philip, Dr Nisha and Waters, Professor Andrew and Billker, Dr Oliver and Modrzynska, Dr Katarzyna
Authors: Kent, R. S., Modrzynska, K. K., Cameron, R., Philip, N., Billker, O., and Waters, A. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Microbiology
Publisher:Nature Publishing Group
ISSN:2058-5276
ISSN (Online):2058-5276
Published Online:03 September 2018
Copyright Holders:Copyright © 2018 Springer Nature
First Published:First published in Nature Microbiology 3(11):1206-1213
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
730171Fellowship for Katarzyna Modrzynska: Dissecting the transcription regulatory network in malaria parasites at early transmission stages.Andrew WatersWellcome Trust (WELLCOTR)202600/Z/16/ZIII - PARASITOLOGY
5887510BBSRC Doctoral Training Partnership 2012George BaillieBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS COLLEGE SENIOR MANAGEMENT
466861Conditional translational repression: a core regulatory mechanism of gene expression during development of the malaria parasite.Andrew WatersWellcome Trust (WELLCOTR)083811/Z/07/ZIII - PARASITOLOGY
690321Gene expression in Plasmodium parasites: the molecular mechanics of gametocytogenesis (and variant transcription of genes)Andrew WatersWellcome Trust (WELLCOTR)107046/Z/15/ZIII - PARASITOLOGY
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY