scholarly journals The pseudogene SURFIN 4.1 is vital for merozoite formation in blood stage P. falciparum

2019 ◽  
Author(s):  
Tatiane Macedo-Silva ◽  
Rosana Beatriz Duque Araujo ◽  
Gerhard Wunderlich
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Family ◽  
Multigene Family ◽  
Malaria Parasite ◽  
Stop Codon ◽  
Blood Stage ◽  
Human Malaria Parasite ◽  
Stop Codons ◽  
Novel Target ◽  
Late Trophozoite

AbstractThe surf gene family of the human malaria parasite Plasmodium falciparum encodes for antigens with largely unknown functions. Three of the ten surf genes found in the P. falciparum 3D7 genome are annotated as pseudogenes, and one of these – surf4.1 (PF3D7_0402200) - was continuously transcribed in P. falciparum 3D7 blood stage forms. GFP-tagging revealed that despite several stop codons a full-length protein was expressed, which localized to developing merozoites. Analysis of cDNAs showed that no specific editing occurred pointing to readthrough of stop codons during translation. Intriguingly, attempts to generate parasite lines containing an additional artificial stop codon failed. Transcript knockdown revealed that surf4.1 is essential for merozoite formation in late trophozoite/schizont stages while DNA replication seemed not to be influenced. SURFIN4.1 is the first example of a plasmodial multigene family member of which a knockout is deleterious and may pose as a novel target for anti-malarial therapy.

scholarly journals A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum

FEBS Letters ◽  
1999 ◽  
Vol 447 (2-3) ◽  
pp. 149-154 ◽  
Author(s):  
Colin Berry ◽  
Michelle J Humphreys ◽  
Philip Matharu ◽  
Rachel Granger ◽  
Paul Horrocks ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Family ◽  
Malaria Parasite ◽  
Aspartic Proteinase ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Distinct Member

Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum

Parasitology ◽  
2000 ◽  
Vol 121 (2) ◽  
pp. 127-133 ◽  
Author(s):  
T. G. SMITH ◽  
P. LOURENÇO ◽  
R. CARTER ◽  
D. WALLIKER ◽  
L. C. RANFORD-CARTWRIGHT
Keyword(s):  
Plasmodium Falciparum ◽  
Sexual Differentiation ◽  
Malaria Parasite ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum

2005 ◽  
Vol 392 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Keizo Yuasa ◽  
Fumika Mi-Ichi ◽  
Tamaki Kobayashi ◽  
Masaya Yamanouchi ◽  
Jun Kotera ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cyclic Nucleotide ◽  
Malaria Parasite ◽  
Catalytic Domain ◽  
Hydrolytic Activity ◽  
Human Malaria Parasite ◽  
Pde Inhibitors ◽  
Ic50 Value ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

This is the first report of molecular characterization of a novel cyclic nucleotide PDE (phosphodiesterase), isolated from the human malaria parasite Plasmodium falciparum and designated PfPDE1. PfPDE1 cDNA encodes an 884-amino-acid protein, including six putative transmembrane domains in the N-terminus followed by a catalytic domain. The PfPDE1 gene is a single-copy gene consisting of two exons and a 170 bp intron. PfPDE1 transcripts were abundant in the ring form of the asexual blood stages of the parasite. The C-terminal catalytic domain of PfPDE1, produced in Escherichia coli, specifically hydrolysed cGMP with a Km value of 0.65 μM. Among the PDE inhibitors tested, a PDE5 inhibitor, zaprinast, was the most effective, having an IC50 value of 3.8 μM. The non-specific PDE inhibitors IBMX (3-isobutyl-1-methylxanthine), theophylline and the antimalarial chloroquine had IC50 values of over 100 μM. Membrane fractions prepared from P. falciparum at mixed asexual blood stages showed potent cGMP hydrolytic activity compared with cytosolic fractions. This hydrolytic activity was sensitive to zaprinast with an IC50 value of 4.1 μM, but insensitive to IBMX and theophylline. Furthermore, an in vitro antimalarial activity assay demonstrated that zaprinast inhibited the growth of the asexual blood parasites, with an ED50 value of 35 μM. The impact of cyclic nucleotide signalling on the cellular development of this parasite has previously been discussed. Thus this enzyme is suggested to be a novel potential target for the treatment of the disease malaria.

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