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Current Opinion in Microbiology Dec 2016Giardia intestinalis is a non-invasive protozoan parasite infecting the upper small intestine causing acute, watery diarrhea or giardiasis in 280 million people... (Review)
Review
Giardia intestinalis is a non-invasive protozoan parasite infecting the upper small intestine causing acute, watery diarrhea or giardiasis in 280 million people annually. Asymptomatic infections are equally common and recent data have suggested that infections even can be protective against other diarrheal diseases. Most symptomatic infections resolve spontaneously but infections can lead to chronic disease and treatment failures are becoming more common world-wide. Giardia infections can also result in irritable bowel syndrome (IBS) and food allergies after resolution. Until recently not much was known about the mechanism of giardiasis or the cause of post-giardiasis syndromes and treatment failures, but here we will describe the recent progress in these areas.
Topics: Animals; Diarrhea; Gastrointestinal Diseases; Giardia; Giardiasis; Host-Parasite Interactions; Humans; Irritable Bowel Syndrome; Treatment Failure
PubMed: 27501461
DOI: 10.1016/j.mib.2016.07.019 -
Trends in Parasitology Jul 2022
Topics: Feces; Genotype; Giardia; Giardia lamblia; Giardiasis; Humans; Prevalence
PubMed: 35074260
DOI: 10.1016/j.pt.2022.01.001 -
Clinical Microbiology Reviews Jul 2001Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron... (Review)
Review
Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5' and 3' untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism.
Topics: Animals; Antigenic Variation; Antigens, Protozoan; Genes, Protozoan; Giardia lamblia; Giardiasis; Host-Parasite Interactions; Humans
PubMed: 11432808
DOI: 10.1128/CMR.14.3.447-475.2001 -
Advances in Parasitology 2020Giardia lamblia is a widespread parasitic protist with a complex MT cytoskeleton that is critical for motility, attachment, mitosis and cell division, and transitions... (Review)
Review
Giardia lamblia is a widespread parasitic protist with a complex MT cytoskeleton that is critical for motility, attachment, mitosis and cell division, and transitions between its two life cycle stages-the infectious cyst and flagellated trophozoite. Giardia trophozoites have both highly dynamic and highly stable MT organelles, including the ventral disc, eight flagella, the median body and the funis. The ventral disc, an elaborate MT organelle, is essential for the parasite's attachment to the intestinal villi to avoid peristalsis. Giardia's four flagellar pairs enable swimming motility and may also promote attachment. They are maintained at different equilibrium lengths and are distinguished by their long cytoplasmic regions and novel extra-axonemal structures. The functions of the median body and funis, MT organelles unique to Giardia, remain less understood. In addition to conserved MT-associated proteins, the genome is enriched in ankyrins, NEKs, and novel hypothetical proteins that also associate with the MT cytoskeleton. High-resolution ultrastructural imaging and a current inventory of more than 300 proteins associated with Giardia's MT cytoskeleton lay the groundwork for future mechanistic analyses of parasite attachment to the host, motility, cell division, and encystation/excystation. Giardia's unique MT organelles exemplify the capacity of MT polymers to generate intricate structures that are diverse in both form and function. Thus, beyond its relevance to pathogenesis, the study of Giardia's MT cytoskeleton informs basic cytoskeletal biology and cellular evolution. With the availability of new molecular genetic tools to disrupt gene function, we anticipate a new era of cytoskeletal discovery in Giardia.
Topics: Giardia; Microtubules; Organelles
PubMed: 32122531
DOI: 10.1016/bs.apar.2019.11.001 -
Clinical Microbiology Reviews Jan 2011Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and... (Review)
Review
Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution of Giardia duodenalis genotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for some G. duodenalis genotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics of G. duodenalis in humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of various G. duodenalis genotypes, and the ecology of environmental contamination.
Topics: Animals; Genotype; Giardia; Giardiasis; Humans; Molecular Epidemiology; Molecular Typing; Parasitology; Zoonoses
PubMed: 21233509
DOI: 10.1128/CMR.00033-10 -
Frontiers in Immunology 2022Human giardiasis, caused by the protozoan parasite (syn. , , ), is one of the most commonly-identified parasitic diseases worldwide. Chronic infections cause a... (Review)
Review
Human giardiasis, caused by the protozoan parasite (syn. , , ), is one of the most commonly-identified parasitic diseases worldwide. Chronic infections cause a malabsorption syndrome that may lead to failure to thrive and/or stunted growth, especially in children in developing countries. Understanding the parasite/epithelial cell crosstalk at the mucosal surfaces of the small intestine during human giardiasis may provide novel insights into the mechanisms underlying the parasite-induced immunopathology and epithelial tissue damage, leading to malnutrition. Efforts to identify new targets for intervening in the development of intestinal immunopathology and the progression to malnutrition are critical. Translating these findings into a clinical setting will require analysis of these pathways in cells and tissues from humans and clinical trials could be devised to determine whether interfering with unwanted mucosal immune responses developed during human giardiasis provide better therapeutic benefits and clinical outcomes for infections in humans.
Topics: Child; Epithelial Cells; Giardia; Giardia lamblia; Giardiasis; Humans; Intestinal Mucosa; Malnutrition
PubMed: 35250996
DOI: 10.3389/fimmu.2022.817468 -
Advances in Parasitology 2012In this review, the current status of genomic and proteomic research on Giardia is examined in terms of evolutionary biology, phylogenetic relationships and taxonomy.... (Review)
Review
In this review, the current status of genomic and proteomic research on Giardia is examined in terms of evolutionary biology, phylogenetic relationships and taxonomy. The review also describes how characterising genetic variation in Giardia from numerous hosts and endemic areas has provided a better understanding of life cycle patterns, transmission and the epidemiology of Giardia infections in humans, domestic animals and wildlife. Some progress has been made in relating genomic information to the phenotype of Giardia, and as a consequence, new information has been obtained on aspects of developmental biology and the host-parasite relationship. However, deficiencies remain in our understanding of pathogenesis and host specificity, highlighting the limitations of currently available genomic datasets.
Topics: Animals; Genetic Variation; Genome, Protozoan; Giardia; Giardiasis; Host-Parasite Interactions; Humans; Phylogeny; Proteome
PubMed: 22520441
DOI: 10.1016/B978-0-12-394303-3.00003-7 -
Advances in Parasitology 2019During the course of giardiasis in humans and experimental models, G. duodenalis trophozoites express and secrete several proteins (ESPs) affecting structural, cellular... (Review)
Review
During the course of giardiasis in humans and experimental models, G. duodenalis trophozoites express and secrete several proteins (ESPs) affecting structural, cellular and soluble components of the host intestinal milieu. These include the toxin-like molecules CRP136 and ESP58 that induce intestinal hyper-peristalsis. After the completion of the Giardia genome database and using up-to date transcriptomic and proteomic approaches, secreted 'virulence factors' have also been identified and experimentally characterized. This repertoire includes arginine deiminase (ADI) that competes for arginine, an important energy source for trophozoites, some high-cysteine membrane proteins (HCMPs) and VSP88, a versatile variant surface protein (VSP) that functions as an extracellular protease. Another giardial protein, enolase, moonlights as a metabolic enzyme that interacts with the fibrinolytic system and damages host epithelial cells. Other putative Giardia virulence factors are cysteine proteases that degrade multiple host components including mucin, villin, tight junction proteins, immunoglobulins, defensins and cytokines. One of these proteases, named giardipain-1, decreases transepithelial electrical resistance and induces apoptosis in epithelial cells. A putative role for tenascins, present in the Giardia's secretome, is interfering with the host epidermal growth factor. Based on the roles that these molecules play, drugs may be designed to interfere with their functions. This review presents a comprehensive description of secreted Giardia virulence factors. It further describes their cytotoxic mechanisms and roles in the pathophysiology of giardiasis, and then assesses their potential as targets for drug development.
Topics: Animals; Epithelial Cells; Giardia; Giardiasis; Humans; Protozoan Proteins; Virulence Factors
PubMed: 31630757
DOI: 10.1016/bs.apar.2019.07.003 -
Advances in Parasitology 1979
Review
Topics: Animals; Cats; Cricetinae; Disease Models, Animal; Dogs; Giardia; Giardiasis; Humans; In Vitro Techniques; Mice; Microscopy, Electron, Scanning; Rats; Terminology as Topic
PubMed: 395833
DOI: 10.1016/s0065-308x(08)60548-5 -
Advances in Parasitology 2020This review considers current advances in tools to investigate the functional biology of Giardia, it's coding and non-coding genes, features and cellular and molecular... (Review)
Review
This review considers current advances in tools to investigate the functional biology of Giardia, it's coding and non-coding genes, features and cellular and molecular biology. We consider major gaps in current knowledge of the parasite and discuss the present state-of-the-art in its in vivo and in vitro cultivation. Advances in in silico tools, including for the modelling non-coding RNAs and genomic elements, as well as detailed exploration of coding genes through inferred homology to model organisms, have provided significant, primary level insight. Improved methods to model the three-dimensional structure of proteins offer new insights into their function, and binding interactions with ligands, other proteins or precursor drugs, and offer substantial opportunities to prioritise proteins for further study and experimentation. These approaches can be supplemented by the growing and highly accessible arsenal of systems-based methods now being applied to Giardia, led by genomic, transcriptomic and proteomic methods, but rapidly incorporating advanced tools for detection of real-time transcription, evaluation of chromatin states and direct measurement of macromolecular complexes. Methods to directly interrogate and perturb gene function have made major leaps in recent years, with CRISPr-interference now available. These approaches, coupled with protein over-expression, fluorescent labelling and in vitro and in vivo imaging, are set to revolutionize the field and herald an exciting time during which the field may finally realise Giardia's long proposed potential as a model parasite and eukaryote.
Topics: Computational Biology; Giardia lamblia; Research
PubMed: 32122532
DOI: 10.1016/bs.apar.2019.12.002