title: Antimalarial iron chelator FBS0701 blocks transmission by Plasmodium falciparum gametocyte activation inhibition.
abstract: Reducing the transmission of the malarial parasite by Anopheles mosquitoes using drugs or vaccines remains a main focus in the efforts to control malaria. Iron chelators have been studied as potential antimalarial drugs due to their activities against different stages of the parasite. The iron chelator FBS0701 affects the development of Plasmodium falciparum early gametocytes and lowers blood-stage parasitemia. Here, we tested the effect of FBS0701 on stage V gametocyte infectivity for mosquitoes. The incubation of stage V gametocytes for up to 3 days with increasing concentrations of FBS0701 resulted in a significant dose-related reduction in mosquito infectivity, as measured by the numbers of oocysts per mosquito. The reduction in mosquito infectivity was due to the inhibition of male and female gametocyte activation. The preincubation of FBS0701 with ferric chloride restored gametocyte infectivity, showing that the inhibitory effect of FBS0701 was quenched by iron. Deferoxamine, another iron chelator, also reduced gametocyte infectivity but to a lesser extent. Finally, the simultaneous administration of drug and gametocytes to mosquitoes without previous incubation did not significantly reduce the numbers of oocysts. These results show the importance of gametocyte iron metabolism as a potential target for new transmission-blocking strategies.
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ferrer
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Vega-Rodriguez
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Abhai K
authors.initials: AK
authors.lastname: Tripathi
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
authors.affiliation: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA dsulliv7@jhmi.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D005019:Ethyl Ethers / Q000494:pharmacology*; D005260:Female; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C572777:4,5-dihydro-2-(2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid; D000962:Antimalarials; D005019:Ethyl Ethers; D007502:Iron Chelating Agents; D013844:Thiazoles; D003676:Deferoxamine