Plasmodium falciparum Gametocyte Development 1 (Pfgdv1) and Gametocytogenesis Early Gene Identification and Commitment to Sexual Development

PLoS Pathogens

Kirakorn Kiattibutr¹  Timothy G. Myers¹  Adebowale Adeyemo²  Tetsuya Furuya²  Belinda J. Morahan²  Huichun Xu²  Beata Czesny²  Saliha Eksi²  Xin-zhuan Su³  Amreena Suri³  Jetsumon Sattabongkot⁴  Omar Ali⁵  Hongying Jiang⁵  Kim C. Williamson⁵  Yoseph Haile⁵ 

[1] Center for Research on Genomics and Global Health, Inherited Disease Research Branch, National Human Genomics Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America;Department of Biology, Loyola University Chicago, Chicago, Illinois, United States of America;Department of Entomology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Gametocytes;    Plasmodium;    Parasitic diseases;    Parasitemia;    Sexual differentiation;    Malaria;    Malarial parasites;    Oligonucleotides;   

DOI  :  10.1371/journal.ppat.1002964

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY