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      Quantitative analysis of P lasmodium ookinete motion in three dimensions suggests a critical role for cell shape in the biomechanics of malaria parasite gliding motility


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          Motility is a fundamental part of cellular life and survival, including for P lasmodium parasites – single‐celled protozoan pathogens responsible for human malaria. The motile life cycle forms achieve motility, called gliding, via the activity of an internal actomyosin motor. Although gliding is based on the well‐studied system of actin and myosin, its core biomechanics are not completely understood. Currently accepted models suggest it results from a specifically organized cellular motor that produces a rearward directional force. When linked to surface‐bound adhesins, this force is passaged to the cell posterior, propelling the parasite forwards. Gliding motility is observed in all three life cycle stages of P lasmodium: sporozoites, merozoites and ookinetes. However, it is only the ookinetes – formed inside the midgut of infected mosquitoes – that display continuous gliding without the necessity of host cell entry. This makes them ideal candidates for invasion‐free biomechanical analysis. Here we apply a plate‐based imaging approach to study ookinete motion in three‐dimensional (3 D) space to understand P lasmodium cell motility and how movement facilitates midgut colonization. Using single‐cell tracking and numerical analysis of parasite motion in 3 D, our analysis demonstrates that ookinetes move with a conserved left‐handed helical trajectory. Investigation of cell morphology suggests this trajectory may be based on the ookinete subpellicular cytoskeleton, with complementary whole and subcellular electron microscopy showing that, like their motion paths, ookinetes share a conserved left‐handed corkscrew shape and underlying twisted microtubular architecture. Through comparisons of 3 D movement between wild‐type ookinetes and a cytoskeleton‐knockout mutant we demonstrate that perturbation of cell shape changes motion from helical to broadly linear. Therefore, while the precise linkages between cellular architecture and actomyosin motor organization remain unknown, our analysis suggests that the molecular basis of cell shape may, in addition to motor force, be a key adaptive strategy for malaria parasite dissemination and, as such, transmission.

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          Quantitative imaging of Plasmodium transmission from mosquito to mammal.

          Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into the dermis and must reach the liver before infecting erythrocytes and causing disease. We present here a quantitative, real-time analysis of the fate of parasites transmitted in a rodent system. We show that only a proportion of the parasites enter blood capillaries, whereas others are drained by lymphatics. Lymph sporozoites stop at the proximal lymph node, where most are degraded inside dendritic leucocytes, but some can partially differentiate into exoerythrocytic stages. This previously unrecognized step of the parasite life cycle could influence the immune response of the host, and may have implications for vaccination strategies against the preerythrocytic stages of the parasite.
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            The silent path to thousands of merozoites: the Plasmodium liver stage.

            Plasmodium sporozoites are deposited in the skin of their vertebrate hosts through the bite of an infected female Anopheles mosquito. Most of these parasites find a blood vessel and travel in the peripheral blood circulation until they reach the liver sinusoids. Once there, the sporozoites cross the sinusoidal wall and migrate through several hepatocytes before they infect a final hepatocyte, with the formation of a parasitophorous vacuole, in which the intrahepatic form of the parasite grows and multiplies. During this period, each sporozoite generates thousands of merozoites. As the development of Plasmodium sporozoites inside hepatocytes is an obligatory step before the onset of disease, understanding the parasite's requirements during this period is crucial for the development of any form of early intervention. This Review summarizes our current knowledge on this stage of the Plasmodium life cycle.
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              The cellular and molecular basis for malaria parasite invasion of the human red blood cell

              Malaria is a major disease of humans caused by protozoan parasites from the genus Plasmodium. It has a complex life cycle; however, asexual parasite infection within the blood stream is responsible for all disease pathology. This stage is initiated when merozoites, the free invasive blood-stage form, invade circulating erythrocytes. Although invasion is rapid, it is the only time of the life cycle when the parasite is directly exposed to the host immune system. Significant effort has, therefore, focused on identifying the proteins involved and understanding the underlying mechanisms behind merozoite invasion into the protected niche inside the human erythrocyte.

                Author and article information

                Cell Microbiol
                Cell. Microbiol
                Cellular Microbiology
                28 March 2014
                May 2014
                : 16
                : 5 , Malaria ( doiID: 10.1111/cmi.2014.16.issue-5 )
                : 734-750
                [ 1 ] Victoria Research Laboratory, National ICT Australia (NICTA) Department of Computing and Information SystemsUniversity of Melbourne Melbourne Vic. 3010Australia
                [ 2 ] Infection and Immunity DivisionThe Walter and Eliza Hall of Institute of Medical Research Parkville Vic. 3052Australia
                [ 3 ] Centre for Dynamic ImagingThe Walter and Eliza Hall of Institute of Medical Research Parkville Vic. 3052Australia
                [ 4 ] Department of Medical BiologyUniversity of Melbourne Vic. 3052Australia
                [ 5 ] Electron Microscopy Unit Bio21 Molecular Science and Biotechnology Institute and Department of Biochemistry and Molecular Biology University of Melbourne Parkville Vic. 3010Australia
                [ 6 ] School of BotanyThe University of Melbourne Parkville Vic. 3010Australia
                [ 7 ] Department of Life SciencesImperial College of Science, Technology and Medicine London SW7 2AZUK
                [ 8 ] Department of Life Sciences Sir Alexander Fleming BuildingImperial College London South Kensington London SW7 2AZUK
                Author notes
                [*] [* ]For correspondence. E‐mail jake.baum@ 123456imperial.ac.uk ; Tel. (+61) 393452476; Fax (+61) 393470852.

                These authors contributed equally.

                © 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Pages: 18
                Funded by: National Health and Medical Research Council of Australia (NHMRC)
                Award ID: 637341
                Award ID: APP1055246
                Funded by: Human Frontier Science Program (HFSP) Young Investigator Program
                Award ID: RGY0071/2011
                Funded by: National ICT Australia (NICTA)
                Funded by: Australian Research Council (ARC)
                Award ID: FT100100112
                Funded by: Wellcome Trust
                Award ID: 100993/Z/13/Z
                Special Issue on Malaria
                Read here for publications from the European Virtual Institute for Malaria Research and the world wide malaria research community commemorating the 10th annual ‘BioMalPar’ meeting on the biology and pathology of the malaria parasite
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                May 2014
                Converter:WILEY_ML3GV2_TO_NLM version:4.0.7 mode:remove_FC converted:25.07.2014

                Microbiology & Virology
                Microbiology & Virology


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