Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei

Robyn S. Kent, Katarzyna K. Modrzynska, Rachael Cameron, Nisha Philip, Oliver Billker, Andrew P. Waters

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

LanguageEnglish
JournalArchives of Microbiology
Early online date3 Sep 2018
DOIs
Publication statusE-pub ahead of print - 3 Sep 2018

Fingerprint

Plasmodium berghei
Sexual Development
Malaria
Parasites
Malaria control
Transcription Factor AP-2
Plasmodium malariae
Transcription
Apicomplexa
Plasmodium
Data acquisition
Blood
Culicidae
Cells
Switches
Rodentia
Erythrocytes
Infection
Population

Keywords

  • malaria
  • Plasmodium berghei
  • microbiology

Cite this

Kent, Robyn S. ; Modrzynska, Katarzyna K. ; Cameron, Rachael ; Philip, Nisha ; Billker, Oliver ; Waters, Andrew P. / Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei. In: Archives of Microbiology. 2018.
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Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei. / Kent, Robyn S.; Modrzynska, Katarzyna K.; Cameron, Rachael; Philip, Nisha; Billker, Oliver; Waters, Andrew P.

In: Archives of Microbiology, 03.09.2018.

Research output: Contribution to journalArticle

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N2 - 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.

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