Plasmodium vivax transcriptomes reveal stage-specific chloroquine response and differential regulation of male and female gametocytes

• Published in: Nature communications 2019-01, Vol.10 (1), p.371-9, Article 371
• Main Authors: Kim, Adam, Popovici, Jean, Menard, Didier, Serre, David
• Format: Article
• Language: English
• Subjects: 38; 38/90; 38/91; 631/326/417/1716; 631/326/88; 631/337/2019; Antimalarials - pharmacology; Cell Cycle - drug effects; Cell Cycle - genetics; Chloroquine; Chloroquine - pharmacology; Female; Gametocytes; Gene expression; Gene Expression Regulation - drug effects; Genes; Genes, Protozoan - drug effects; Genes, Protozoan - genetics; Genome, Protozoan - drug effects; Genome, Protozoan - genetics; Humanities and Social Sciences; Humans; Infections; Life Sciences; Malaria; Malaria - drug therapy; Malaria, Falciparum - drug therapy; Malaria, Vivax - drug therapy; Male; Microbiology and Parasitology; multidisciplinary; Multigene Family; Parasites; Parasitology; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium vivax; Plasmodium vivax - drug effects; Plasmodium vivax - genetics; Plasmodium vivax - pathogenicity; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Transcriptome - drug effects; Trophozoites; Trophozoites - drug effects; Trophozoites - genetics; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08312-z

Studies of Plasmodium vivax gene expression are complicated by the lack of in vitro culture system and the difficulties associated with studying clinical infections that often contain multiple clones and a mixture of parasite stages. Here, we characterize the transcriptomes of P. vivax parasites from 26 malaria patients. We show that most parasite mRNAs derive from trophozoites and that the asynchronicity of P. vivax infections is therefore unlikely to confound gene expression studies. Analyses of gametocyte genes reveal two distinct clusters of co-regulated genes, suggesting that male and female gametocytes are independently regulated. Finally, we analyze gene expression changes induced by chloroquine and show that this antimalarial drug efficiently eliminates most P. vivax parasite stages but, in contrast to P. falciparum , does not affect trophozoites. Plasmodium vivax biology is not well understood, due to a lack of in vitro culture systems and difficulties associated with studying clinical blood samples. Here, Kim et al. use gene expression profiles from P. vivax infected patient blood and show stage-specific chloroquine response and differential regulation of male and female gametocytes.