scholarly journals Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector

mBio ◽  
2021 ◽  
Author(s):  
Sudhir Kumar ◽  
Meseret T. Haile ◽  
Michael R. Hoopmann ◽  
Linh T. Tran ◽  
Samantha A. Michaels ◽  
...  

Transmission of the malaria parasite to the mosquito vector is critical for the completion of the sexual stage of the parasite life cycle and is dependent on the release of male gametes from the gametocyte body inside the mosquito midgut. In the present study, we demonstrate that PfCDPK4 is critical for male gametogenesis and is involved in phosphorylation of proteins essential for male gamete emergence.

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4203
Author(s):  
Héloïse Débare ◽  
Nathalie Moiré ◽  
Firmin Baron ◽  
Louis Lantier ◽  
Bruno Héraut ◽  
...  

Treatments currently used to prevent congenital toxoplasmosis are non-specific of Toxoplasma gondii and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-b]pyridazine salt targeting the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis. Swiss mice were infected at mid-pregnancy with tachyzoites or cysts of the ME49 strain of T. gondii by intraperitoneal and oral route, respectively, and treated with SP230 at 50 mg/kg for 5 days by the same routes. Parasite burden in organs of dams and in foetuses was measured by quantitative PCR. Intraperitoneal administration of SP230 drastically reduced the number of parasites (more than 97% of reduction) in the brain and lungs of dams, and led to a reduction of 66% of parasite burden in foetuses. Oral administration of SP230 was particularly efficient with 97% of reduction of parasite burdens in foetuses. SP230 did not impact number and weight of offspring in our conditions. This inhibitor of TgCDPK1 is a promising candidate for the development of alternative therapeutics to treat infected pregnant women.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80818 ◽  
Author(s):  
Fei Chen ◽  
Marianna Fasoli ◽  
Giovanni Battista Tornielli ◽  
Silvia Dal Santo ◽  
Mario Pezzotti ◽  
...  

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 433 ◽  
Author(s):  
Xiangpei Kong ◽  
Wei Lv ◽  
Shanshan Jiang ◽  
Dan Zhang ◽  
Guohua Cai ◽  
...  

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