Giardia duodenalis, also known as Giardia intestinalis and Giardia lamblia, is a flagellated parasitic protozoan microorganism of the genus Giardia that colonizes the small intestine, causing a diarrheal condition known as giardiasis. The parasite attaches to the intestinal epithelium by a ventral disc (syn. adhesive disc or sucker), and reproduces via binary fission. G. duodenalis is a non-invasive parasite, that does not spread to other parts of the gastrointestinal tract, but remains confined to the lumen of the small intestine. The parasite exists in two forms; trophozoites and cysts. The microorganism can undergo encystation, transforming into a dormant cyst that enables it to survive outside of its host. Giardia trophozoites are anaerobic, and absorb their nutrients from the intestinal lumen. If the organism is stained, its characteristic pattern resembles the familiar "smiley face" symbol.

Chief pathways of human infection include ingestion of untreated drinking water (which is the most common method of transmission for this parasite),

Almost half of those infected with giardiasis remain asymptomatic. For those who do experience symptoms, they usually appear 1 to 2 weeks after infection. Common symptoms include abdominal pain, nausea, and bloating, along with large, watery, foul-smelling, and greasy stools. Due to frequent loose stools, individuals with giardiasis often experience dehydration. It has also been shown that G. intestinalis damages the intestinal epithelium, which directly affects nutrient absorption.

Life cycle

thumb|Lifecycle of Giardia lamblia

G. duodenalis takes on two morphologically distinct forms during its lifecycle. Trophozoites are the replicative stage of the parasite, characterized by a pear-shaped, motile, flagellated cell that survives only in the small intestine of the host. The trophozoites do not penetrate host cells, but rather attaches to the intestinal epithelium cells to establish an infection. A cyst is the environmentally stable stage of the parasite, that facilitates transmission between hosts. Some trophozoites differentiate back into cysts under specific conditions, such as high organism density. The cysts remain dormant until ingested by a host animal. When a new potential host ingests water or food contaminated with this feces, the cysts gain entry to the gastrointestinal tract of the new host, repeating the cycle.

Structure

The trophozoite has an elaborate structure with two nuclei and four pairs of flagella which allow it to swim within the intestinal lumen of the host. It also has an adhesive disk on its ventral surface that is associated with the parasite's attachment to the intestinal epithelium. The adhesive disk is composed of microtubules, and is found only in Giardia. The parasite lacks Golgi apparatus and mitochondria but has mitosomes, which probably evolved from mitochondria. The mitosome is a double-membraned organelle, that lacks the enzymatic components required for classic mitochondrial functions, such as ATP synthesis and lipid metabolism. However, they do contain certain mitochondrial genes associated with iron-sulfur complex biosynthesis, which suggests that this organism likely lost its mitochondria during evolution.

The cyst can survive for weeks to months in cold water, They may also occur in city reservoirs and persist after water treatment, as the cysts are resistant to conventional water-treatment methods, such as chlorination and ozonolysis. Giardia duodenalis is common around the world because the parasite resides in bodies of water; typically rivers, lakes, and recreational swimming pools. Giardiasis is more prevalent in developing countries, where the sanitation and overall hygiene is poorer compared to developed countries. In developed nations, giardiasis has a prevalence of 2–5%, whereas in developing nations it is significantly higher, ranging from 20% to 30%. In the United States, it has been discovered that a majority of whom are infected by the Giardia duodenalis parasite tend to reside in more urban areas, and, patients who are infected are more likely to live in the Southern United States.

Ecology

Giardia infects humans, but is also one of the most common parasites infecting cats, dogs, and birds. Mammalian hosts also include dozens of species, including cattle, sheep,

Cats can be cured easily, and lambs usually simply lose weight, but in calves, the parasites can be fatal and often are not responsive to antibiotics or electrolytes. Carriers among calves can also be asymptomatic. This parasite is deadly for chinchillas, so extra care must be taken by providing them with safe water. Dogs have a high infection rate, as 30% of the population under one year old are known to be infected in kennels. The infection is more prevalent in puppies than in adult dogs. Infected dogs can be isolated and treated, or the entire pack at a kennel can be presumptively treated together. Kennels and areas used for exercise should be considered contaminated for at least one month after dogs show signs of infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by quarantine of infected dogs for at least 20 days and careful management and maintenance of a clean water supply.

Cell biology

thumb|Giardia trophozoites stained with Giemsa; 100x magnification

G. duodenalis trophozoites are pear-shaped cells, 15 μm long, 8 μm across, and 3 μm thick. They are motile by way of four pairs of flagella, which propel the trophozoites through the intestine. Trophozoites about to differentiate into cysts also contain prominent vesicles termed encystation-specific vesicles that disappear once cyst wall construction begins. Each cell also contains a pair of rigid structures called median bodies which make up part of the G. lamblia cytoskeleton. As in mitochondria, proteins with a certain peptide signal sequence are trafficked to and imported into the mitosome. Unlike mitochondria, mitosomes have no genome of their own. All mitosomal genes are encoded by the Giardia nuclear genome. The genome has been sequenced and was published in 2007, although the sequence contains several gaps. The sequence is about 12 million base pairs and contains about 5000 protein-coding genes. The GC-content is 46%. Trophozoites have a ploidy of four and the ploidy of cysts is eight, which in turn raises the question of how Giardia maintains homogeneity between the chromosomes of the same and opposite nuclei. Modern sequencing technologies have been used to resequence different strains. Eight genotype assemblages of G. duodenalis have been recognized to date (A-H). The T-cell response in giardiasis includes T helper cells and cytotoxic T cells, and the production of IgA by B cells also helps to eliminate the infection.

Evolution

Giardia had been assumed to be primitively asexual and with no means of transferring DNA between nuclei. These assumptions made explaining the remarkably low level of allelic heterozygosity (< 0.01%) in the genome isolate, WB, very difficult, but all those assumptions of asexuality are now in doubt, with population genetics providing evidence for recombination and the identification of meiotic genes, evidence for recombination among isolates and the evidence for exchange of genetic material between nuclei during the process of encystation.

These findings on sexuality in Giardia, above, have important implications for understanding the origin of sexual reproduction in eukaryotes. Though sexual reproduction is widespread among extant eukaryotes, until recently, sex seemed unlikely to be a primordial and fundamental feature of eukaryotes. A probable reason for the view that sex may not be fundamental to eukaryotes was that sexual reproduction previously appeared to be lacking in certain human pathogenic single-celled eukaryotes (e.g. Giardia) that diverged from early ancestors in the eukaryotic lineage.

In addition to the evidence cited above for recombination in Giardia, Malik et al. reported that many meiosis specific genes occur in the Giardia genome, and further that homologs of these genes also occur in another unicellular eukaryote, Trichomonas vaginalis. Because these two species are descendants of lineages that are highly divergent among eukaryotes, Malik et al. proposed, based on phylogenetic analysis, that facultative sex was present in the common ancestor of all eukaryotes. Bernstein et al. also reviewed evidence in support of this view.

Research

Frances Gillin of the University of California, San Diego, and her colleagues cultivated the entire lifecycle of this parasite in the laboratory, and identified biochemical cues in the host's digestive system that trigger Giardias lifecycle transformations. They also uncovered several ways in which the parasite evades the defenses of the infected organism. One of these is by altering the proteins on its surface, which confounds the ability of the infected animal's immune system to detect and combat the parasite (called antigenic variation). Gillin's work reveals why Giardia infections are extremely persistent and prone to recur. In addition, these insights into its biology and survival techniques may enable scientists to develop better strategies to understand, prevent, and treat Giardia infections.

In December 2008, Nature published an article showing the discovery of an RNA interference mechanism that allows Giardia to switch variant-specific surface proteins to avoid host immune response. The discovery was made by the team working at the Biochemistry and Molecular Biology Laboratory, School of Medicine, Catholic University of Cordoba, Argentina, led by Dr. Hugo Lujan.

In 2022, a study conducted by Elisa Barroeta-Echegaray and colleagues concluded that Giardia duodenalis secretes enolase as a monomer during the interaction, or attachment, of trophozoites with intestinal epithelial cells. This interaction was shown to activate plasminogen and induce necroptotic damage in intestinal epithelial cells. Blocking the enolase inhibited trophozoite attachment to intestinal epithelial cells. Enolase was also shown to enhance plasmin activity, leading to significant cell damage characterized by vacuolization and intercellular separation. Enolase also induced necroptosis in epithelial cells via tumor necrosis factor α (TNF-α) and apoptosis-inducing factor (AIF), independent of caspase-3 activity. These findings suggest that Giardia enolase is a critical virulence factor in host-pathogen interactions. Constitutively expressed Cas9 nuclease in combination with a cassette bearing the recombining knock-out construct, allows to knock out all four alleles of interest in the trophozoite stage in vitro. Complementation and protein tagging are also available to study protein localization and function in Giardia. Making cysts in vitro is also possible, for example using the Uppsala encystation protocol. Excystation in vitro is also possible, although viable trophozoite numbers are quite low after excystation in vitro.

The main congress about Giardia is the International Giardia and Cryptosporidium Conference. A summary of results presented at the most recent editions (2019, in Rouen, France and 2025, in Melbourne, Australia) are available.

History

thumb|A Giardia trophozoite, drawn by Vilém Lambl and published in 1859

thumb|left|Drawings of a Giardia trophozoite and cyst by Charles E. Simon in 1921

The first likely description of Giardia was in 1681 by Antonie van Leeuwenhoek, who in a letter to Robert Hooke, described "animalcules" resembling Giardia trophozoites in his stool. The next known description of Giardia wasn't until 1859, when Czech physician Vilém Lambl published a description of the trophozoite stages he saw in the stool of a pediatric patient. Lambl termed the organism Cercomonas intestinalis. In 1888, Raphaël Blanchard renamed the parasite Lamblia intestinalis in Lambl's honor. In 1921, Charles E. Simon published a detailed description of the parasite's morphology.

See also

  • List of parasites of humans

References

  • Giardia lamblia image library
  • GiardiaDB: The Giardia lamblia genome sequencing project
  • Washington State Department of Health fact sheet on Giardia.
  • Centers for Disease Control and Prevention (CDC) Giardia Information
  • United States Environmental Protection Agency fact sheet on Giardia in water
  • Giardia article at MicrobeWiki
  • Video of Giardia Life Cycle
  • Giardia and the Sierra Nevada
  • [http://diarrhea.emedtv.com/giardia-lamblia/giardia-lambia.html]