Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes |
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Authors: | Svetlana Glushakova Josh R. Beck Matthias Garten Brad L. Busse Armiyaw S. Nasamu Tatyana Tenkova‐Heuser John Heuser Daniel E. Goldberg Joshua Zimmerberg |
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Affiliation: | 1. Section on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;2. Division of Infectious Diseases, Department of Medicine, Washington University, St. Louis, Missouri;3. Department of Biomedical Sciences, Iowa State University, Ames, Iowa |
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Abstract: | Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting membranes. Parasite Ca2+, kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here, the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live‐cell microscopy of parasites expressing PV‐targeted fluorescent proteins, and specific egress inhibitors. Several minutes before egress, under control of parasite [Ca2+]i, the PV began rounding. Then after ~1.5 min, under control of PfPKG and SUB1, there was abrupt rupture of the PV membrane and release of vacuolar contents. Over the next ~6 min, there was progressive vacuolar membrane deterioration simultaneous with erythrocyte membrane distortion, lasting until the final minute of the egress programme when newly formed parasites mobilised and erythrocyte membranes permeabilised and then ruptured—a dramatic finale to the parasite cycle of replication. |
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Keywords: | infection membrane microbial structure microbial– cell interaction parasitophorous vacuole Plasmodium falciparum |
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