- Review Article
- Published:
Gliding motility powers invasion and egress in Apicomplexa
Nature Reviews Microbiologyvolume 15, pages645–660 (2017)Cite this article
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Key Points
Apicomplexa are unicellular eukaryotic parasites that exhibit two types of secretory organelle at their apical pole and a membranous system that underlies their plasma membrane.
Apicomplexa are obligate intracellular parasites that use a substrate-dependent gliding motility to move and to actively enter host cells, and to egress from the infected cells.
Motility by Apicomplexa relies on the translocation of parasite surface adhesins from the apical pole, from where they are secreted to the posterior pole in a process powered by a machinery termed the glideosome. The rearward translocation of the adhesins bound to host cell receptors involves the actomyosin system, which propels the parasite forward.
The invasion of host cells involves the formation of a moving junction at the point of apposition between the plasma membrane of the parasite and the host cell. Both ligands and receptors are secreted by the parasite, and they form a solid platform to support the force applied by the parasite during penetration.
A tightly regulated signalling cascade coordinates the apical secretion of microneme proteins and the activation of the glideosome, which leads to gliding motility.
Abstract
Protozoan parasites have developed elaborate motility systems that facilitate infection and dissemination. For example, amoebae use actin-rich membrane extensions called pseudopodia, whereas Kinetoplastida are propelled by microtubule-containing flagella. By contrast, the motile and invasive stages of the Apicomplexa — a phylum that contains the important human pathogensPlasmodium falciparum (which causes malaria) andToxoplasma gondii (which causes toxoplasmosis) — have a unique machinery called the glideosome, which is composed of an actomyosin system that underlies the plasma membrane. The glideosome promotes substrate-dependent gliding motility, which powers migration across biological barriers, as well as active host cell entry and egress from infected cells. In this Review, we discuss the discovery of the principles that govern gliding motility, the characterization of the molecular machinery involved, and its impact on parasite invasion and egress from infected cells.
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Acknowledgements
The authors thank H. Bullen and D. Jacot for critical reading of the manuscript. They are grateful to M. Blackman and J. Thomas, and to F. Frischknecht and M. Brochet, for providing the movies of merozoite egress and invasion, and of sporozoite and ookinete motility, respectively. During the manuscript revision process, 25% of the text and references had to be removed owing to space constraints. The authors apologize that not all relevant studies could not be discussed and cited as a result of this. K.F. is supported by the Swiss National Foundation (FN3100A0-116722) and received funding from the Sir Jules Thorn Charitable Overseas Trust reg., Schaan subsidy for young researchers. M.L. received funding from the Laboratoire d'Excellence (LabEx; ParaFrap ANR-11-LABX-0024). D.S.-F. is an advanced international scholar of the Howard Hughes Medical Institute.
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Authors and Affiliations
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CMU, 1 Rue Michel-Servet, Geneva 4, 1211, Switzerland
Karine Frénal & Dominique Soldati-Favre
Unité Mixte de Recherche 5235 – Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier, Place Eugène Bataillon, Montpellier cedex 5, 34095, France
Jean-François Dubremetz & Maryse Lebrun
- Karine Frénal
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- Jean-François Dubremetz
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- Maryse Lebrun
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- Dominique Soldati-Favre
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Contributions
D.S-F., K.F., J-F.D. and M.L. all contributed to the writing of this Review, and D.S-F., K.F. and M.L. worked on the review and editing of the manuscript before submission.
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Correspondence toKarine Frénal orDominique Soldati-Favre.
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Supplementary information
Supplementary information S6 (table)
Summary of proteins functionally shown to be involved in apicomplexan motility, invasion or egress (DOC 378 kb)
Supplementary Movie S1
Circular gliding ofPlasmodium berghei sporozoite. Movie courtesy of F. Frischknecht, Centre for Infectious Diseases, Heidelberg University Hospital, Germany. (AVI 490 kb)
Supplementary Movie S2
Circular gliding ofToxoplasma gondii tachyzoite (AVI 317 kb)
Supplementary Movie S3
Helical gliding ofToxoplasma gondii tachyzoite (AVI 811 kb)
Supplementary Movie S4
Stationary twirling ofToxoplasma gondii tachyzoite (AVI 507 kb)
Supplementary Movie S5
Gliding ofPlasmodium berghei ookinetes. Movie courtesy of M. Brochet, Faculty of Medicine, University of Geneva, Switzerland. (AVI 809 kb)
Supplementary Movie S7
Egress and invasion ofPlasmodium falciparum merozoites. Movie courtesy of M. Blackman and J. Thomas, The Francis Crick Institute, London, United Kingdom. (MOV 174 kb)
Glossary
- Apicomplexa
A phylum of diverse, single-celled, eukaryotic, obligate intracellular parasites.
- Alveolata
A group of protists within the kingdom Eukarya that contains the phyla Dinoflagellata, Ciliophora and Apicomplexa.
- Toxoplasmosis
A food-borne infection caused by the parasiteToxoplasma gondii. The infection is usually mild or even asymptomatic, but can have serious consequences in patients who are immunocompromised and for the fetus in the case of primary infection during pregnancy.
- Sporozoites
The infectious and motile stage produced in oocysts and transmitted by the definitive host.
- Tachyzoites
The motile and fast-replicative stage ofToxoplasma gondii that is able to invade any nucleated cell in the host.
- Merozoites
The stage ofPlasmodium spp. that infects erythrocytes, in which it initiates a new asexual life cycle.
- Actomyosin system
A complex that comprises actin filaments, myosin and associated proteins, and that is involved in movement.
- Glideosome
A molecular complex that powers gliding motility in apicomplexan parasites.
- Circumsporozoite precipitation reaction
A reaction in which sporozoites, incubated in immune serum, eject a tail-like precipitate in a process that corresponds to the shedding of the glycosylphosphatidylinositol-anchored circumsporozoite protein crosslinked by antibodies.
- Cytochalasin
A type of fungal metabolite that inhibits actin polymerization. Cytochalasin A and cytochalasin B can have pleiotropic effects, which include the inhibition of monosaccharide uptake and transport.
- Coccidia
A subclass of Apicomplexa comprising parasites that infect the intestinal tracts of animals, such asToxoplasma gondii,Neospora spp.,Eimeria spp. andSarcocystis spp. These parasites harbour an apical structure, termed a conoid, that consists of anticlockwise spiralling fibres.
- Gregarina
Large apicomplexan parasites that are∼0.5 mm in size and are capable of infecting terrestrial and marine invertebrates.
- Moving junction
An intimate junction made at the point of apposition between the parasite and host cell plasma membranes. It is also referred to as a tight junction or circular junction in the literature.
- Pellicle
In apicomplexans, the three-layered structure comprising the plasma membrane and the underlying inner membrane complex.
- Inner membrane complex
(IMC). In apicomplexans, one or more flattened vesicular sacs, also named alveoli, that are visible as double-membranous structures underneath the plasma membrane. The IMC is composed of only one alveolus inPlasmodium spp. or of a patchwork of alveoli inToxoplasma gondii orEimeria spp.
- Rhoptries
Club-shaped secretory organelles that are located at the apical pole of parasites and are composed of two subcompartments: the neck and the bulb.
- Micronemes
Elliptic secretory organelles that are located at the apical pole of parasites.
- Actin-binding proteins
(ABPs). Proteins that bind to globular and/or filamentous actin and influence, for example, monomer sequestration or delivery, filament nucleation, polymerization, depolarization, stability and capping.
- Myosin
A molecular motor that binds to cargo and converts chemical energy released by ATP hydrolysis into directed movement along tracks of actin filaments.
- Acylation
The co-translational or post-translational addition of a lipid onto protein residues; examples include myristoylation (in which a 14-carbon saturated fatty acid is added onto a glycine residue at position 2) and palmitoylation (in which a 16-carbon saturated fatty acid is added onto a cysteine residue).
- Conoid
A cone-shaped, apical structure that is present in coccidian parasites and is made of spirally arranged tubulin fibres. The conoid protrudes in a calcium-dependent manner during motility, invasion and egress.
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Frénal, K., Dubremetz, JF., Lebrun, M.et al. Gliding motility powers invasion and egress in Apicomplexa.Nat Rev Microbiol15, 645–660 (2017). https://doi.org/10.1038/nrmicro.2017.86
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