Giardia intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, but the disease mechanisms have been poorly understood until recently.
Giardia spp. are some of the most divergent eukaryotes examined to date and provide unique opportunities for gaining basic insights into key pathways that characterize eukaryotic cells and also for identifying new molecular mechanisms.
Cell differentiation in Giardia spp. involves two major developmental transitions: from the ingested, dormant cyst via the excyzoite to trophozoites, in a process known as excystation, and from the motile, replicating trophozoite back to the infective cyst, in a process known as encystation.
Mitosomes in Giardia spp. are elongated, double-membraned organelles that are related to mitochondria, and their only known function is in the assembly of Fe–S clusters.
Giardia spp., like all diplomonads, have two nuclei. These nuclei have been shown to be equivalent in size and in the amount of DNA that they contain, and both are transcriptionally active.
Analyses of Giardia spp. genomes indicate that these organisms encode rudimentary forms of many cellular processes, with fewer subunits present in simplified cellular machineries, and have a limited metabolic repertoire with many bacterial-like enzymes that were introduced by horizontal gene transfer.
The adhesive disc and the four flagella of the pathogen, together with differentiation and antigenic variation of the variant-specific surface proteins (VSPs), are the major virulence factors identified to date for Giardia spp. Epigenetic mechanisms, microRNAs and RNA interference have been shown to be important in the regulation of vsp gene expression.
Several mechanisms (including epithelial-barrier dysfunction, apoptosis, diffuse shortening of microvilli, hypersecretion of Cl− and inhibition of brush-border enzymes) have been proposed to be important for the induction of symptoms during giardial infection, and the cause of giardiasis is probably multifactorial.
The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. In this Review we discuss recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis.
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S.G.S. is supported by the Swedish Research Council VR–M, the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas) and the Swedish International Development Cooperation Agency (SIDA).
The authors declare no competing financial interests.
Entrez Genome Project
The resistant, transmissive form of the giardial parasite.
- Relic organelle
A cellular organelle that has evolved into a reduced form with fewer or novel functions.
A short-lived stage of the giardial parasite that initiates infection.
The replicating, disease-causing form of the giardial parasite.
- Fe–S cluster
An essential cofactor of proteins that are involved in catalysis and electron transport. A cluster contains a sulphide-linked di-, tri- or tetra-iron centre that can exist in one of several oxidation states.
- Allelic sequence heterozygosity
The sequence difference between different alleles of the same gene.
- Intrinsic pathway
An apoptotic pathway in which the crucial step is the permeabilization of the outer mitochondrial membrane.
- Extrinsic pathway
An apoptotic pathway that is mediated by the binding of an extracellular ligand to a transmembrane receptor.
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Ankarklev, J., Jerlström-Hultqvist, J., Ringqvist, E. et al. Behind the smile: cell biology and disease mechanisms of Giardia species. Nat Rev Microbiol 8, 413–422 (2010). https://doi.org/10.1038/nrmicro2317
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