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      Regulation of Sexual Commitment and Gametocytogenesis in Malaria Parasites

      Author(s): 1 , 2 , 3 , 1 , 2 , 4
      Publication date Created:
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      Journal: Annual Review of Microbiology
      Publisher: Annual Reviews

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          Abstract

          Sexual differentiation of malaria parasites from the asexual blood stage into gametocytes is an essential part of the life cycle, as gametocytes are the form that is taken up by the mosquito host. Because of the essentiality of this process for transmission to the mosquito, gametocytogenesis is an extremely attractive target for therapeutic interventions. The subject of this review is the considerable progress that has been made in recent years in elucidating the molecular mechanisms governing this important differentiation process. In particular, a number of critical transcription factors and epigenetic regulators have emerged as crucial elements in the regulation of commitment. The identification of these factors has allowed us to understand better than ever before the events occurring prior to and during commitment to sexual development and offers potential for new therapeutic interventions.

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          Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination.

          Teun Bousema, Chris Drakeley (2011)
          Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.
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            Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

            Ellen Bushell, Ana Rita Gomes, Theo Sanderson … (2017)
            Summary The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of Plasmodium parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.
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              Regulation of sexual development of Plasmodium by translational repression.

              G Mair (2006)
              Translational repression of messenger RNAs (mRNAs) plays an important role in sexual differentiation and gametogenesis in multicellular eukaryotes. Translational repression and mRNA turnover were shown to influence stage-specific gene expression in the protozoan Plasmodium. The DDX6-class RNA helicase, DOZI (development of zygote inhibited), is found in a complex with mRNA species in cytoplasmic bodies of female, blood-stage gametocytes. These translationally repressed complexes are normally stored for translation after fertilization. Genetic disruption of pbdozi inhibits the formation of the ribonucleoprotein complexes, and instead, at least 370 transcripts are diverted to a degradation pathway.
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                Author and article information

                Journal
                Title: Annual Review of Microbiology
                Abbreviated Title: Annu. Rev. Microbiol.
                Publisher: Annual Reviews
                ISSN (Print): 0066-4227
                ISSN (Electronic): 1545-3251
                Publication date Created: September 08 2018
                Publication date (Print): September 08 2018
                Volume: 72
                Issue: 1
                Pages: 501-519
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA;
                [2 ]Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania 16802, USA
                [3 ]Microbiology and Immunology Department, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
                [4 ]Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA
                Article
                DOI: 10.1146/annurev-micro-090817-062712
                PMC ID: 7164540
                PubMed ID: 29975590
                SO-VID: cea3eb1d-2282-47dc-928a-11b2daa44912
                Copyright © © 2018
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