Journal Article

Behind the smile: cell biology and disease mechanisms of Giardia species

Ringqvist, Emma, Svärd, Staffan G., Ankarklev, Johan, Jerlström-Hultqvist, Jon, Troell, Karin

2010

Overview

Key Points 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. In addition to being a major worldwide contributor to diarrhoeal disease, Giardia intestinalis is a useful model system for studying basic eukaryotic cellular processes owing to its reduced complexity. Here, Svärd and colleagues review the recent advances in our understanding of giardial cell biology and pathogenesis. 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 .

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/417/2546 / 631/80/304 / 692/699/255/1715 / Adhesives / Animals / Antigenic Variation / Biologi / Biology / Biomedical and Life Sciences / Causes of / Cell division / Cysts / Cytoskeleton / Diagnosis / Diarrhea - microbiology / Gene expression / Genomes / Giardia / Giardia intestinalis / Giardia lamblia / Giardia lamblia - cytology / Giardia lamblia - growth & development / Giardia lamblia - pathogenicity / Giardiasis / Giardiasis - etiology / Giardiasis - parasitology / Health aspects / Humans / Infections / Infectious Diseases / Kinases / Life Cycle Stages / Life Sciences / Mammals / Medical Microbiology / Microbiology / Mikrobiologi / NATURAL SCIENCES / NATURVETENSKAP / Organism biology / Organismbiologi / Parasites / Parasitology / Phylogeny / Physiological aspects / Proteins / Protozoa / review-article / Trophozoites - cytology / Virology / Virulence Factors - classification