Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes
Abstract Background Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends i...
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ftdoajarticles:oai:doaj.org/article:052407c118844f7b90bfad1333b9a876 2023-05-15T15:17:49+02:00 Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes Glushakova Svetlana Lizunov Vladimir Blank Paul S Melikov Kamran Humphrey Glen Zimmerberg Joshua 2013-01-01T00:00:00Z https://doi.org/10.1186/1475-2875-12-41 https://doaj.org/article/052407c118844f7b90bfad1333b9a876 EN eng BMC http://www.malariajournal.com/content/12/1/41 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-12-41 1475-2875 https://doaj.org/article/052407c118844f7b90bfad1333b9a876 Malaria Journal, Vol 12, Iss 1, p 41 (2013) Plasmodium falciparum Asexual cycle of replication Parasite egress Free calcium Swelling of parasitophorous vacuole Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2013 ftdoajarticles https://doi.org/10.1186/1475-2875-12-41 2022-12-31T03:29:55Z Abstract Background Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca 2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca 2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca 2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Methods Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca 2+ homeostasis on the egress programme. Results A steady increase in cytoplasmic free Ca 2+ is found to precede parasite egress. This increase is independent of extracellular Ca 2+ for at least the last two hours of the cycle, but is dependent upon Ca 2+ release from internal stores. Intracellular BAPTA chelation of Ca 2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca 2+ -ATPase accelerate parasite egress, indicating that Ca 2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca 2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca 2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. Conclusions The parasite egress programme requires intracellular free Ca 2+ for egress ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 12 1 41 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Plasmodium falciparum Asexual cycle of replication Parasite egress Free calcium Swelling of parasitophorous vacuole Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium falciparum Asexual cycle of replication Parasite egress Free calcium Swelling of parasitophorous vacuole Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Glushakova Svetlana Lizunov Vladimir Blank Paul S Melikov Kamran Humphrey Glen Zimmerberg Joshua Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
topic_facet |
Plasmodium falciparum Asexual cycle of replication Parasite egress Free calcium Swelling of parasitophorous vacuole Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca 2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca 2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca 2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Methods Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca 2+ homeostasis on the egress programme. Results A steady increase in cytoplasmic free Ca 2+ is found to precede parasite egress. This increase is independent of extracellular Ca 2+ for at least the last two hours of the cycle, but is dependent upon Ca 2+ release from internal stores. Intracellular BAPTA chelation of Ca 2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca 2+ -ATPase accelerate parasite egress, indicating that Ca 2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca 2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca 2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. Conclusions The parasite egress programme requires intracellular free Ca 2+ for egress ... |
format |
Article in Journal/Newspaper |
author |
Glushakova Svetlana Lizunov Vladimir Blank Paul S Melikov Kamran Humphrey Glen Zimmerberg Joshua |
author_facet |
Glushakova Svetlana Lizunov Vladimir Blank Paul S Melikov Kamran Humphrey Glen Zimmerberg Joshua |
author_sort |
Glushakova Svetlana |
title |
Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
title_short |
Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
title_full |
Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
title_fullStr |
Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
title_full_unstemmed |
Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
title_sort |
cytoplasmic free ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes |
publisher |
BMC |
publishDate |
2013 |
url |
https://doi.org/10.1186/1475-2875-12-41 https://doaj.org/article/052407c118844f7b90bfad1333b9a876 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 12, Iss 1, p 41 (2013) |
op_relation |
http://www.malariajournal.com/content/12/1/41 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-12-41 1475-2875 https://doaj.org/article/052407c118844f7b90bfad1333b9a876 |
op_doi |
https://doi.org/10.1186/1475-2875-12-41 |
container_title |
Malaria Journal |
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12 |
container_issue |
1 |
container_start_page |
41 |
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1766348084439154688 |