Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development

Malaria transmission requires the production of male and female gametocytes in the human host followed by fertilization and sporogonic development in the mosquito midgut. Although essential for the spread of malaria through the population, little is known about the initiation of gametocytogenesis in...

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Bibliographic Details
Published in:PLoS pathogens 2012-10, Vol.8 (10), p.e1002964-e1002964
Main Authors: Eksi, Saliha, Morahan, Belinda J, Haile, Yoseph, Furuya, Tetsuya, Jiang, Hongying, Ali, Omar, Xu, Huichun, Kiattibutr, Kirakorn, Suri, Amreena, Czesny, Beata, Adeyemo, Adebowale, Myers, Timothy G, Sattabongkot, Jetsumon, Su, Xin-zhuan, Williamson, Kim C
Format: Article
Language:English
Subjects:
Biology
Cell development (Biology)
Gametocytes
Gene expression
Gene Expression Regulation, Developmental
Genes
Genes, Protozoan
Genetic aspects
Health aspects
Humans
Malaria
Malaria - parasitology
Malaria - transmission
Medicine
Microbial genetics
Mosquitoes
Parasitemia
Parasites
Physiological aspects
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - growth & development
Plasmodium falciparum - metabolism
Proteins
Protozoan Proteins - blood
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Reproduction, Asexual
Transcription, Genetic
Transcriptome
Virulence (Microbiology)
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Summary:Malaria transmission requires the production of male and female gametocytes in the human host followed by fertilization and sporogonic development in the mosquito midgut. Although essential for the spread of malaria through the population, little is known about the initiation of gametocytogenesis in vitro or in vivo. Using a gametocyte-defective parasite line and genetic complementation, we show that Plasmodium falciparumgametocyte development 1 gene (Pfgdv1), encoding a peri-nuclear protein, is critical for early sexual differentiation. Transcriptional analysis of Pfgdv1 negative and positive parasite lines identified a set of gametocytogenesis early genes (Pfge) that were significantly down-regulated (>10 fold) in the absence of Pfgdv1 and expression was restored after Pfgdv1 complementation. Progressive accumulation of Pfge transcripts during successive rounds of asexual replication in synchronized cultures suggests that gametocytes are induced continuously during asexual growth. Comparison of Pfge gene transcriptional profiles in patient samples divided the genes into two groups differing in their expression in mature circulating gametocytes and providing candidates to evaluate gametocyte induction and maturation separately in vivo. The expression profile of one of the early gametocyte specific genes, Pfge1, correlated significantly with asexual parasitemia, which is consistent with the ongoing induction of gametocytogenesis during asexual growth observed in vitro and reinforces the need for sustained transmission-blocking strategies to eliminate malaria.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002964