Immunity to Sexual Stages of Malaria Parasites

2015 ◽  
pp. 193-214 ◽  
Author(s):  
Richard Carter ◽  
Nirbhay Kumar ◽  
Isabella Quakyi ◽  
Michael Good ◽  
Kamini Mendis ◽  
...  
Keyword(s):  
Malaria Parasites ◽  
Sexual Stages

scholarly journals 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes

2021 ◽  
Author(s):  
Meng Liu ◽  
Gangqiang Guo ◽  
Pengge Qian ◽  
Jianbing Mu ◽  
Binbin Lu ◽  
...  
Keyword(s):  
Translation Efficiency ◽  
Biological Processes ◽  
Malaria Parasites ◽  
Single Nucleotide ◽  
Dynamic Regulation ◽  
Knock Out ◽  
Transcript Stability ◽  
Sexual Stages ◽  
Nucleotide Resolution ◽  
Single Nucleotide Resolution

5-methylcytosine (m5C) is an important epi-transcriptomic modification involved in mRNA stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (P. yoelii) and human (P. falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knock-out of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in rodent and human malaria parasites. Restoration of the nsun2 gene in the knock-out parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.

Immunity to Sexual Stages of Malaria Parasites

1988 ◽  
pp. 193-214 ◽  
Author(s):  
Richard Carter ◽  
Nirbhay Kumar ◽  
Isabella Quakyi ◽  
Michael Good ◽  
Kamini Mendis ◽  
...  
Keyword(s):  
Malaria Parasites ◽  
Sexual Stages

scholarly journals Plasmodium falciparumgametocytes: with a view to a kill

Parasitology ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 1718-1734 ◽  
Author(s):  
ALICE S. BUTTERWORTH ◽  
TINA S. SKINNER-ADAMS ◽  
DON L. GARDINER ◽  
KATHARINE R. TRENHOLME
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Discovery ◽  
Malaria Control ◽  
Asexual Parasite ◽  
Malaria Parasites ◽  
Gametocyte Carriage ◽  
Control Programmes ◽  
Development Pipeline ◽  
Malaria Eradication ◽  
Sexual Stages

SUMMARYDrugs that kill or inhibit the sexual stages ofPlasmodiumin order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control ofPlasmodium falciparumtransmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.

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