Building the Perfect Parasite: Cell Division in Apicomplexa

PLoS Pathogens, May 2022

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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Building the Perfect Parasite: Cell Division in Apicomplexa

van Dooren GG (2007) Building the perfect parasite: Cell division in Apicomplexa. PLoS Pathog 3(6): e78. doi:10.1371/journal. ppat.0030078 Building the Perfect Parasite: Cell Division in Apicomplexa Boris Striepen 0 1 Carly N. Jordan 0 1 Sarah Reiff 0 1 Giel G. van Dooren 0 1 0 Boris Striepen is with the Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology, University of Georgia , Athens , Georgia , United States of America. Giel G. van Dooren is with the Center for Tropical and Emerging Global Diseases, University of Georgia , Athens , Georgia , United States of America. Carly N. Jordan and Sarah Reiff are with the Department of Cellular Biology, University of Georgia , Athens, Georgia , United States of America 1 Editor: B. Brett Finlay, University of British Columbia , Canada A toxoplasmosis, and crytposporidiosis in humans, and picomplexans are pathogens responsible for malaria, 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. - A wide variety of prokaryotic and eukaryotic pathogens have evolved the ability to invade and replicate within the cells of their hosts. Few have developed the level of sophistication and control exerted by the members of the Apicomplexa [1]. Upon contact with a suitable host cell, apicomplexans can invade within seconds, with minimal apparent disturbance of the infected cell (Figure 1). This process is dependent on actin and myosin and is driven by parasite and not host motility [2,3]. Tightly associated with host cell penetration is the secretion of three distinct parasite organelles: rhoptries, micronemes, and dense granules. Secretion is timed in succession, and secreted proteins play key roles in adhesion, motility and formation, and elaboration of the parasitophorous vacuole, a new cellular compartment established during invasion that the parasite occupies during its intracellular development (see [4,5] for detailed reviews of this process in Toxoplasma and Plasmodium, respectively). The cellular structure of the zoite, the non-replicative extracellular stage, appears streamlined towards one goal: finding and invading the next host cell. Zoites are found at various stages of the apicomplexan life cycle and are the product of asexual as well as sexual replication processes (see Figure 1A for a simplified apicomplexan life cycle). The zoite is highly polarized, with the apical tip containing the organizing center for the subpellicular microtubles that run along the longitudinal axis of the parasite [6]. This axis also polarizes the cells motility, driving the parasite into host cells with its apex first. In some species, the tip is further elaborated by the conoid, a cytoskeletal structure that is built from a unique, tightly wound tubulin polymer and is extended during invasion and motility [7]. Importantly, the apical end is also the site for rhoptry and microneme secretion, with these organelles tightly packed into the anterior portion of the cell. While the anterior of the zoite is focused on invasion, the rest of cell carries the genetic material and tools to grow and develop once in the host cell, including a nucleus and a single mitochondrion, plastid, and Golgi. Divide and Conquer 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 (...truncated)


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Boris Striepen, Carly N Jordan, Sarah Reiff, Giel G van Dooren. Building the Perfect Parasite: Cell Division in Apicomplexa, PLoS Pathogens, 2007, 6, DOI: https://doi.org/10.1371/journal.ppat.0030078