A chloroplast-like organelle is present in many species of the Apicomplexa phylum. We have previously demonstrated that the plastid organelle of Plasmodium faciparum is essential to the survival of the blood-stage
malaria parasite in culture. One known function of the plastid organelle in another Apicomplexan, Toxoplasma gondii, involves the formation of the parasitophorous vacuole. The effects of interruption of plastid function on sporozoites and sexual-stage parasites have not been investigated. In our previous studies of the effects of
thiostrepton, a
polypeptide antibiotic from streptococcus spp., on erythrocytic schizongony of the human
malaria P. falciparium, we found that this
antibiotic appears to interact with the
guanosine triphosphatase (
GTPase) binding domain of the organellar large subunit ribosomal
RNA, as it does in bacteria. We investigate here the effects of this
drug on life-cycle stages of the
malaria parasite in vivo. Preincubation of mature infective sporozoites with
thiostrepton has no observable effect on their infectivity. Sporozoite
infection both by mosquito
bite and sporozoite injection was prevented by pretreatment of mice with
thiostrepton.
Thiostrepton eliminates
infection with erythrocytic forms of Plasmodium berghei in mice. Clearance of infected red blood cells follows the delayed kinetics associated with drugs that interact with the apicoplast.
Thiostrepton treatment of infected mice reduces transmission of parasites by more than ten-fold, indicating that the plastid has a role in sexual development of the parasite. These results indicate that the plastid function is accessible to
drug action in vivo and important to the development of both sexual and asexual forms of the parasite.