Molecular complexity of sexual development and gene regulation in Plasmodium falciparum

Kumar, Nirbhay; Cha, Gloria; Pineda, Fernando; Maciel, Jorge; Haddad, Diana; Bhattacharyya, Mrinal Kanti; Nagayasu, Eiji

doi:10.1016/j.ijpara.2004.10.013

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…The rapid morphological transformations between the different developmental stages in the life cycle of Plasmodium imply that developmental progression is highly regulated (Florens et al ., 2002; Le Roch et al ., 2003). However, little is known about the mechanism of gene regulation, no clear promoter has been defined yet and the few cis ‐acting functional motifs identified share no homologies to known eukaryotic promoter or enhancer elements (Kumar et al ., 2004). Whole genome annotation of Plasmodium falciparum revealed a paucity of proteins associated with the transcriptional process implying that mechanisms other than transcriptional control play a major role in the expression of Plasmodium genes.…”

Section: Introductionmentioning

confidence: 99%

Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression

Pace

Olivieri

Sanchez

et al. 2006

Molecular Microbiology

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SummaryTransmission of the malaria parasite depends on specialized gamete precursors (gametocytes) that develop in the bloodstream of a vertebrate host. Gametocyte/gamete differentiation requires controlled patterns of gene expression and regulation not only of stage and gender-specific genes but also of genes associated with DNA replication and mitosis. Once taken up by mosquito, male gametocytes undergo three mitotic cycles within few minutes to produce eight motile gametes. Here we analysed, in two Plasmodium species, the expression of SET, a conserved nuclear protein involved in chromatin dynamics. SET is expressed in both asexual and sexual blood stages but strongly accumulates in male gametocytes. We demonstrated functionally the presence of two distinct promoters upstream of the set open reading frame, the one active in all blood stage parasites while the other active only in gametocytes and in a fraction of schizonts possibly committed to sexual differentiation. In ookinetes both promoters exhibit a basal activity, while in the oocysts the gametocyte-specific promoter is silent and the reporter gene is only transcribed from the constitutive promoter. This transcriptional control, described for the first time in Plasmodium , provides a mechanism by which single-copy genes can be differently modulated during parasite development. In male gametocytes an overexpression of SET might contribute to a prompt entry and execution of S/M phases within mosquito vector.

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Section: Introductionmentioning

confidence: 99%

Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression

Pace

Olivieri

Sanchez

et al. 2006

Molecular Microbiology

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“…The first is to search for motifs identified in other organisms and listed in TRANSFAC. Various laboratories have looked for known motifs in the P. falciparum genome 55 and have been unable to find much of interest, which is probably due to divergence from the other organisms in the database and the unusually high AT content of this genome. AT-rich motifs, a telltale characteristic of regulatory regions in other organisms, occur randomly throughout the P. falciparum genome.…”

Section: Next Stepsmentioning

confidence: 99%

Mechanisms of Gene Regulation in Plasmodium

Deitsch

Duraisingh²,

Dzikowski³

et al. 2007

The American Journal of Tropical Medicine and Hygiene

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“…amodiaquine derivatives resulted in potent antimalarial agents [16], particularly, 5'-fluoroamodiaquine (6), which has proven to be a very potent drug in in vitro and in vivo studies. Moreover, isoquine (7), which is an isomer of amodiaquine, showed a very potent activity as an antimalarial agent. A more detailed discussion on fluorine-containing amodiaquine derivatives is described below.…”

Section: Molecular Targetsmentioning

confidence: 99%

“…Merozoites invade erythrocytes, initiating the asexual stage. Once the oocyst rupture takes place, sporozoites move to the salivary glands, where they are able to invade the mammalian host [6][7][8]. After schizonts rupture and erythrocytes lysis, merozoites are released into the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

Current Status and Progresses Made in Malaria Chemotherapy

Liñares

Rodríguez

2007

CMC

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Malaria is the most important parasitic disease worldwide, affecting more than 500 million people and causing close to 1 million deaths per annum. This serious fact is mainly attributable to the emergence of drug resistant strains of Plasmodium falciparum. The advances made in malaria chemotherapy based on unique aspects of the biochemistry and physiology of the responsible agents for this disease, parasites of Plasmodium genus, are covered in this review. Increasing resistance to conventional antimalarial drugs constitutes the main drawback for the persistence of this disease. In the present article, a comprehensive analysis of selected molecular targets is depicted in terms of their potential utility as chemotherapeutic agents. Our review focuses on different and important molecular targets for drug design that include proteases that hydrolyze hemoglobin, protein farnesyltransferase, heme detoxification pathway, polyamine pathways, dihydrofolate reductase, artemisinin-based combination therapies (ACTs), etc. Therefore, rational approaches to control malaria targeting metabolic pathways of malaria parasites which are essential for parasites survival are presented.

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Molecular complexity of sexual development and gene regulation in Plasmodium falciparum

Cited by 6 publications

References 44 publications

Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression

Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression

Mechanisms of Gene Regulation in Plasmodium

Current Status and Progresses Made in Malaria Chemotherapy

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