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Building the perfect parasite: cell division in apicomplexa.

Striepen B, Jordan CN, Reiff S, van Dooren GG - PLoS Pathog. (2007)

Bottom Line: Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation.Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group?This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

View Article: PubMed Central - PubMed

Affiliation: Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America. striepen@cb.uga.edu

ABSTRACT
Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering from the immune response in the cells of their hosts, while at the same time tapping into these cells as source of nutrients. The complexity and beauty of the structures formed during their intracellular development have made apicomplexans the darling of electron microscopists. Dramatic technological progress over the last decade has transformed apicomplexans into respectable genetic model organisms. Extensive genomic resources are now available for many apicomplexan species. At the same time, parasite transfection has enabled researchers to test the function of specific genes through reverse and forward genetic approaches with increasing sophistication. Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation. Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group? This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

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The Diversity of Intracellular Development in Apicomplexans(A) In T. gondii, two daughters are formed during budding. IMC1, red; MORN1, green (reproduced with permission from [32]).(B) T. gondii. Histone H2, red; IMC3, green (reproduced from [71]).(C) In Plasmodium falciparum liver schizont, budding results in massive numbers of zoites. Image courtesy of Volker Heussler.(D) T. gondii, phase contrast image of parasitophorous vacuole harboring multiple tachyzoites.(E and F) P. falciparum late erythrocyte schizont. Acyl carrier protein (plastid), green. RBC, red blood cell.(G–I) Sarcocystis neurona. Two intracellular stages with polyploid nuclei, one in interphase and one during mitosis. Tubulin, red.(J) S. neurona budding. IMC3, green.(K) A Theileria schizont divides in association with its host cell. Polymorphic immunodominant molecule (parasite surface), green; γ-tubulin (host centrosomes), red. HN, host nucleus. Image courtesy of Dirk Dobbelaere. The DNA dye DAPI is shown in blue throughout. Not to scale.
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ppat-0030078-g002: The Diversity of Intracellular Development in Apicomplexans(A) In T. gondii, two daughters are formed during budding. IMC1, red; MORN1, green (reproduced with permission from [32]).(B) T. gondii. Histone H2, red; IMC3, green (reproduced from [71]).(C) In Plasmodium falciparum liver schizont, budding results in massive numbers of zoites. Image courtesy of Volker Heussler.(D) T. gondii, phase contrast image of parasitophorous vacuole harboring multiple tachyzoites.(E and F) P. falciparum late erythrocyte schizont. Acyl carrier protein (plastid), green. RBC, red blood cell.(G–I) Sarcocystis neurona. Two intracellular stages with polyploid nuclei, one in interphase and one during mitosis. Tubulin, red.(J) S. neurona budding. IMC3, green.(K) A Theileria schizont divides in association with its host cell. Polymorphic immunodominant molecule (parasite surface), green; γ-tubulin (host centrosomes), red. HN, host nucleus. Image courtesy of Dirk Dobbelaere. The DNA dye DAPI is shown in blue throughout. Not to scale.

Mentions: While invasive zoites are similar across the phylum, intracellular stages differ dramatically in size, shape, and architecture (see Figure 2 for a selection of micrographs). The basis for this diversity lies in the flexibility of the apicomplexan cell cycle. Apicomplexans are able to dissociate and variably mix and match three elements that follow each other invariably in most other cells: DNA replication and chromosome segregation, nuclear division, and, lastly, cytokinesis or budding (see Figure 3 for a schematic). While Toxoplasma completes all elements of the cycle after each round of DNA replication, Plasmodium and Sarcocystis forgo cytokinesis and/or nuclear divisions for multiple cycles, forming stages that are multinucleate or contain a single polyploid nucleus (these division modes are also known as endodyogeny, schizogony, and endopolyogeny [8–10]). Dramatic differences in the division mode also occur between different life cycle stages in a single species; asexual stages of Toxoplasma in the cat intestine, for example, divide by endodyogeny and endopolygeny [11]. In each case, however, the development will culminate in the emergence of multiple invasive zoites, which seek new host cells to invade. Apicomplexans of the genus Theileria are a surprising exception to this divide and conquer scenario. Theileria sporozoites remain in the lymphocyte that they initially invade, where they amplify in numbers without resorting to leaving the shelter of the host cell. The key to this trick lies in this parasite's ability to transform the host cell through manipulation of the NFκB pathway. The parasite assembles and activates a mammalian IKK signalosome on its surface, promoting unchecked host cell replication [12,13]. Theileria also interacts with host cell microtubules, enabling these parasites to migrate to, and apparently latch onto, host cell centrosomes. This results in partitioning of parasites into forming daughter cells of the host, exploiting the host's mitotic spindle (see Figures 2 and 3; [12,14]; and D. Dobbelaere, personal communication).


Building the perfect parasite: cell division in apicomplexa.

Striepen B, Jordan CN, Reiff S, van Dooren GG - PLoS Pathog. (2007)

The Diversity of Intracellular Development in Apicomplexans(A) In T. gondii, two daughters are formed during budding. IMC1, red; MORN1, green (reproduced with permission from [32]).(B) T. gondii. Histone H2, red; IMC3, green (reproduced from [71]).(C) In Plasmodium falciparum liver schizont, budding results in massive numbers of zoites. Image courtesy of Volker Heussler.(D) T. gondii, phase contrast image of parasitophorous vacuole harboring multiple tachyzoites.(E and F) P. falciparum late erythrocyte schizont. Acyl carrier protein (plastid), green. RBC, red blood cell.(G–I) Sarcocystis neurona. Two intracellular stages with polyploid nuclei, one in interphase and one during mitosis. Tubulin, red.(J) S. neurona budding. IMC3, green.(K) A Theileria schizont divides in association with its host cell. Polymorphic immunodominant molecule (parasite surface), green; γ-tubulin (host centrosomes), red. HN, host nucleus. Image courtesy of Dirk Dobbelaere. The DNA dye DAPI is shown in blue throughout. Not to scale.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1904476&req=5

ppat-0030078-g002: The Diversity of Intracellular Development in Apicomplexans(A) In T. gondii, two daughters are formed during budding. IMC1, red; MORN1, green (reproduced with permission from [32]).(B) T. gondii. Histone H2, red; IMC3, green (reproduced from [71]).(C) In Plasmodium falciparum liver schizont, budding results in massive numbers of zoites. Image courtesy of Volker Heussler.(D) T. gondii, phase contrast image of parasitophorous vacuole harboring multiple tachyzoites.(E and F) P. falciparum late erythrocyte schizont. Acyl carrier protein (plastid), green. RBC, red blood cell.(G–I) Sarcocystis neurona. Two intracellular stages with polyploid nuclei, one in interphase and one during mitosis. Tubulin, red.(J) S. neurona budding. IMC3, green.(K) A Theileria schizont divides in association with its host cell. Polymorphic immunodominant molecule (parasite surface), green; γ-tubulin (host centrosomes), red. HN, host nucleus. Image courtesy of Dirk Dobbelaere. The DNA dye DAPI is shown in blue throughout. Not to scale.
Mentions: While invasive zoites are similar across the phylum, intracellular stages differ dramatically in size, shape, and architecture (see Figure 2 for a selection of micrographs). The basis for this diversity lies in the flexibility of the apicomplexan cell cycle. Apicomplexans are able to dissociate and variably mix and match three elements that follow each other invariably in most other cells: DNA replication and chromosome segregation, nuclear division, and, lastly, cytokinesis or budding (see Figure 3 for a schematic). While Toxoplasma completes all elements of the cycle after each round of DNA replication, Plasmodium and Sarcocystis forgo cytokinesis and/or nuclear divisions for multiple cycles, forming stages that are multinucleate or contain a single polyploid nucleus (these division modes are also known as endodyogeny, schizogony, and endopolyogeny [8–10]). Dramatic differences in the division mode also occur between different life cycle stages in a single species; asexual stages of Toxoplasma in the cat intestine, for example, divide by endodyogeny and endopolygeny [11]. In each case, however, the development will culminate in the emergence of multiple invasive zoites, which seek new host cells to invade. Apicomplexans of the genus Theileria are a surprising exception to this divide and conquer scenario. Theileria sporozoites remain in the lymphocyte that they initially invade, where they amplify in numbers without resorting to leaving the shelter of the host cell. The key to this trick lies in this parasite's ability to transform the host cell through manipulation of the NFκB pathway. The parasite assembles and activates a mammalian IKK signalosome on its surface, promoting unchecked host cell replication [12,13]. Theileria also interacts with host cell microtubules, enabling these parasites to migrate to, and apparently latch onto, host cell centrosomes. This results in partitioning of parasites into forming daughter cells of the host, exploiting the host's mitotic spindle (see Figures 2 and 3; [12,14]; and D. Dobbelaere, personal communication).

Bottom Line: Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation.Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group?This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

View Article: PubMed Central - PubMed

Affiliation: Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America. striepen@cb.uga.edu

ABSTRACT
Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering from the immune response in the cells of their hosts, while at the same time tapping into these cells as source of nutrients. The complexity and beauty of the structures formed during their intracellular development have made apicomplexans the darling of electron microscopists. Dramatic technological progress over the last decade has transformed apicomplexans into respectable genetic model organisms. Extensive genomic resources are now available for many apicomplexan species. At the same time, parasite transfection has enabled researchers to test the function of specific genes through reverse and forward genetic approaches with increasing sophistication. Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation. Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group? This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

Show MeSH
Related in: MedlinePlus