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

Autor: Tetsuya Furuya, Beata Czesny, Yoseph Haile, Omar Ali, Kirakorn Kiattibutr, Saliha Eksi, Hongying Jiang, Belinda Joan Morahan, Adebowale Adeyemo, Xin-zhuan Su, Huichun Xu, Jetsumon Sattabongkot, Amreena Suri, Kim C. Williamson, Timothy G. Myers
Rok vydání: 2012
Předmět:
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 8, Iss 10, p e1002964 (2012)
ISSN: 1553-7374
Popis: 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 falciparum gametocyte 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.
Author Summary As malaria control efforts move toward eradication it becomes increasingly important to develop interventions that block transmission. Consequently, advances are needed in our understanding of the production of gametocytes, which are required to transmit the disease. This report provides a first view of the initial stages of gametocytogenesis in vitro and in vivo and demonstrates that during each asexual replication cycle a subpopulation of parasites convert to gametocyte development providing a long transmission window. We also identify a gene that is critical for gametocyte production, P. falciparum gametocyte development 1 (Pfgdv1) and a set of genes specifically expressed during early gametocytogenesis in P. falciparum (Pfge genes). The expression profile and peri-nuclear location of Pfgdv1 in a subpopulation of schizonts is consistent with a role in an early step in gametocytogenesis. The RNA levels of Pfgdv1 and the Pfge genes accumulated gradually over several asexual cycles in vitro suggesting ongoing gametocyte formation during asexual growth. The further evaluation of these genes in a cohort of malaria infected patients indicated they are good candidates for markers to distinguish ring stage parasites committed to gametocyte production from circulating mature gametocytes, allowing direct analysis of the initiation of sexual differentiation in vivo.
Databáze: OpenAIRE
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