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      The role of cGMP signalling in regulating life cycle progression of  Plasmodium

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          Abstract

          The 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented.

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          A proteomic view of the Plasmodium falciparum life cycle.

          Laurence Florens, Michael Washburn, J. Raine … (2002)
          The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression.
          Article 0 comments Cited 313 times – based on 0 reviews     Review now
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            Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito.

            O. Billker, V Lindo, M Panico … (1998)
            Malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes. Within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. Induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 degrees C below that of the vertebrate host, and a rise in pH from 7.4 to 8.0-8.2. In vivo the mosquito bloodmeal has a pH of between 7.5 and 7.6. It is thought that in vivo the second inducer is an unknown mosquito-derived gametocyte-activating factor. Here we show that this factor is xanthurenic acid. We also show that low concentrations of xanthurenic acid can act together with pH to induce gametogenesis in vitro. Structurally related compounds are at least ninefold less effective at inducing gametogenesis in vitro. In Drosophila mutants with lesions in the kynurenine pathway of tryptophan metabolism (of which xanthurenic acid is a side product), no alternative active compound was detected in crude insect homogenates. These data could form the basis of the rational development of new methods of interrupting the transmission of malaria using drugs or new refractory mosquito genotypes to block parasite gametogenesis.
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              Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes.

              Sharon Yeoh, Rebecca O'Donnell, Konstantinos Koussis … (2007)
              The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte.
              Article 0 comments Cited 124 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Microbes Infect
                Journal ID (iso-abbrev): Microbes Infect
                Title: Microbes and Infection / Institut Pasteur
                Publisher: Elsevier
                ISSN (Print): 1286-4579
                ISSN (Electronic): 1769-714X
                Publication date PMC-release: August 2012
                Publication date (Print): August 2012
                Volume: 14
                Issue: 10-2
                Pages: 831-837
                Affiliations
                Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
                Author notes
                [∗ ]Corresponding author. david.baker@ 123456lshtm.ac.uk
                Article
                Publisher ID: MICINF3889
                DOI: 10.1016/j.micinf.2012.04.011
                PMC ID: 3484397
                PubMed ID: 22613210
                SO-VID: 060dd7d9-14ca-4dde-a757-cef6a7572fc4
                Copyright © © 2012 Elsevier Masson SAS.
                License:

                This document may be redistributed and reused, subject to certain conditions.

                History
                Date received : 3 February 2012
                Date accepted : 17 April 2012
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: schizont,malaria,egress,kinase,gametocyte,merozoite
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: schizont, malaria, egress, kinase, gametocyte, merozoite

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