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    Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse inPlasmodium falciparumegress

    Hale, V.L. and Watermeyer, Jean and Hackett, F. and Vizcay-Barrena, G. and van Ooij, C. and Thomas, J.A. and Spink, M.C. and Harkiolaki, M. and Duke, E. and Fleck, R.A. and Blackman, M.J. and Saibil, Helen R. (2017) Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse inPlasmodium falciparumegress. Proceedings of the National Academy of Sciences of the United States of America 114 (13), pp. 3439-3444. ISSN 0027-8424.

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    Abstract

    In the asexual blood stages of malarial infection, merozoites invade erythrocytes and replicate within a parasitophorous vacuole to form daughter cells that eventually exit (egress) by sequential rupture of the vacuole and erythrocyte membranes. The current model is that PKG, a malarial cGMP-dependent protein kinase, triggers egress, activating malarial proteases and other effectors. Using selective inhibitors of either PKG or cysteine proteases to separately inhibit the sequential steps in membrane perforation, combined with video microscopy, electron tomography, electron energy loss spectroscopy, and soft X-ray tomography of mature intracellular Plasmodium falciparum parasites, we resolve intermediate steps in egress. We show that the parasitophorous vacuole membrane (PVM) is permeabilized 10–30 min before its PKG-triggered breakdown into multilayered vesicles. Just before PVM breakdown, the host red cell undergoes an abrupt, dramatic shape change due to the sudden breakdown of the erythrocyte cytoskeleton, before permeabilization and eventual rupture of the erythrocyte membrane to release the parasites. In contrast to the previous view of PKG-triggered initiation of egress and a gradual dismantling of the host erythrocyte cytoskeleton over the course of schizont development, our findings identify an initial step in egress and show that host cell cytoskeleton breakdown is restricted to a narrow time window within the final stages of egress.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): malaria, egres,s electron tomography, soft X-ray microscopy, electron energy loss spectroscopy
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 29 Jun 2017 08:48
    Last Modified: 04 Sep 2017 14:30
    URI: http://eprints.bbk.ac.uk/id/eprint/19009

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