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      Revisiting gametocyte biology in malaria parasites

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          ABSTRACT

          Gametocytes are the only form of the malaria parasite that is transmissible to the mosquito vector. They are present at low levels in blood circulation and significant knowledge gaps exist in their biology. Recent reductions in the global malaria burden have brought the possibility of elimination and eradication, with renewed focus on malaria transmission biology as a basis for interventions. This review discusses recent insights into gametocyte biology in the major human malaria parasite, Plasmodium falciparum and related species.

          Abstract

          This review provides an update on our current understanding of the only parasite stage that can transmit malaria from man to mosquito, the gametocyte.

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          Discovery of gene function by expression profiling of the malaria parasite life cycle.

          Karine G Le Roch, Yingyao Zhou, Peter Blair … (2003)
          The completion of the genome sequence for Plasmodium falciparum, the species responsible for most malaria human deaths, has the potential to reveal hundreds of new drug targets and proteins involved in pathogenesis. However, only approximately 35% of the genes code for proteins with an identifiable function. The absence of routine genetic tools for studying Plasmodium parasites suggests that this number is unlikely to change quickly if conventional serial methods are used to characterize encoded proteins. Here, we use a high-density oligonucleotide array to generate expression profiles of human and mosquito stages of the malaria parasite's life cycle. Genes with highly correlated levels and temporal patterns of expression were often involved in similar functions or cellular processes.
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            Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

            Jane M-R Carlton, John H. Adams, Joana C. Silva … (2008)
            The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
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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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                Author and article information

                Journal
                Journal ID (nlm-ta): FEMS Microbiol Rev
                Journal ID (iso-abbrev): FEMS Microbiol. Rev
                Journal ID (publisher-id): femsre
                Title: FEMS Microbiology Reviews
                Publisher: Oxford University Press
                ISSN (Print): 0168-6445
                ISSN (Electronic): 1574-6976
                Publication date (Electronic): 09 April 2019
                Publication date Collection: July 2019
                Publication date PMC-release: 09 April 2019
                Volume: 43
                Issue: 4
                Pages: 401-414
                Affiliations
                [1 ]Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Road, Glasgow G12 8TA, UK
                [2 ]Core Facilities, Microscopy Area, Instituto Superiore di Sanita, Via Regina Elena 299, 00161 Rome, Italy
                [3 ]Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA
                Author notes
                Corresponding author: Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Road, Glasgow G12 8TA, UK. Tel: +44 1413303689; E-mail: Matthias.Marti@ 123456glasgow.ac.uk
                Author information
                http://orcid.org/0000-0003-3140-5847
                http://orcid.org/0000-0003-1040-9566
                Article
                Publisher ID: fuz010
                DOI: 10.1093/femsre/fuz010
                PMC ID: 6606849
                PubMed ID: 31220244
                SO-VID: b5b55915-f206-48cc-a9ff-054a38e2d63a
                Copyright © © FEMS 2019.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 14 December 2018
                Date accepted : 05 April 2019
                Page count
                Pages: 14
                Funding
                Funded by: Wellcome Senior Investigator
                Funded by: European Research Council 10.13039/501100000781
                Funded by: Royal Society Wolfson Merit
                Funded by: DFG postdoctoral fellowship
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: plasmodium falciparum,gametocyte,malaria,transmission
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: plasmodium falciparum, gametocyte, malaria, transmission

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