Giardia duodenalis Laura Rojas-López ,1 Rafael C. Marques ,1 and Staffan G. Svärd 1,2, * 1 Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden 2 SciLifeLab, Uppsala University, Sweden TrendsTrendsininParasitologyParasitology Giardia duodenalis (syn. Giardia lamblia and Giardia intestinalis) is a major cause of parasite-induced diarrheal disease. It is found worldwide but the prevalence is higher in low-income countries. Transmission occurs via the fecal–oral route, and sources of G. duodenalis infection include contaminated water or food, or direct contact with infected people or animals. Cysts are immediately infectious upon excretion in feces. After ingestion of the cysts, motile trophozoites emerge (excystation) and attach to intestinal epithelial cells of the upper small intestine where they replicate extracellularly. Giardia completes its life cycle by forming cysts (encystation) in the lower intestinal region. Replication of the parasite can result in profuse, fatty diarrhea in infected individuals, but asymptomatic infections are also common. The major drug used for treatment is metronidazole, but resistance is an emerging problem. Intestinal lumenIntestinal lumen Lamina propriaLamina propria 2 5 3 4 9 ADI Chemokines Cysteine Proteases NO Nutrients IgA 10 Cl Cl Cl 7 8 L-Arginine Cysteine proteases Muc2 Villin 2 1 1 3 5 4 8 7 6 9Arginine starvation and reduced nitric oxide (NO) Microvilli shortening, destruction and malabsorption Chemokine upregulation and recruitment of immune cells 6 Increased intestinal permeability; bacterial and antigen translocation Induction of apoptosis Chemokine degradation Disruption of apical junction complex Disruption of mucin integrity 10 Alteration in microbiota Increased chloride secretion Immune cells Antigenic variation 11 11 Antigenic variation OCT Variable surface proteins (V SPs) Cytosol Cell membrane production TrendsTrendsininParasitologyParasitology KEY FACTS: G. duodenalis is grouped into eight different assemblages (genotypes A–H) based on host specificity and genetic differences. Assemblages A and B infect humans, and certain subgenotypes have zoonotic potential. A small genome (12.6 Mbp with 4963 protein-encoding genes), divided on five different chromosomes in two nuclei (tetraploid organism). The highly reduced mitochondria-like organelles (mitosomes) lack DNA. Recent advances: complete reference genomes, tractable life cycle in vitro, genetic engineering producing knockouts (Cre/LoxP, CRISPR/Cas9) and knockdowns (morpholinos and CRISPRi), culture with organoids and mouse and gerbil models to study immunity and pathogenesis. DISEASE FACTS: Giardia infections can result in a wide range of symptoms, including profuse, fatty diarrhea, abdominal cramps, nausea, and wasting; however, infections can also be subclinical. Chronic infection may cause a disturbed intestinal balance with changes in the microbiota, villus blunting, leaky gut, nutrient malabsorption, and stunted growth. Postinfectious problems include food allergies, irritable bowel syndrome, and chronic fatigue syndrome. Giardia infection induces robust innate and adaptive immune responses, but in contrast to most other intestinal infections, it causes low level or no inflammation. TAXONOMY AND CLASSIFICATION: PHYLUM: Metamonada CLASS: Fornicata ORDER: Diplomonadida FAMILY: Hexamitidae GENUS: Giardia SPECIES: G. duodenalis *Correspondence: Staffan.svard@icm.uu.se (S.G. Svärd). Trends in Parasitology, July 2022, Vol. 38, No. 7 © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1016/j.pt.2022.01.001 605 Trends in Parasitology | Parasite of the Month Acknowledgment Our work on Giardia is supported by grants from the Swedish Research Council to S.G.S. and a Consejo Nacional de Ciencia y Tecnología (CONACyT) scholarship to L.R.L. Declaration of interests The authors declare no competing interests. Resources www.cdc.gov/parasites/giardia/index.html https://giardiadb.org/giardiadb/ Literature 1. Adam, R.D. (2021) Giardia duodenalis: Biology and pathogenesis. Clin. Microbiol. Rev., e0002419 2. Caccio, S.M. et al. (2018) Host specificity in the Giardia duodenalis species complex. Infect. Genet. Evol. 66, 335–345 3. Rogawski, E.T. et al. (2018) Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study. Lancet Glob. Health 6, e1319–e1328 4. Riba, A. et al. (2020) Disturbed gut microbiota and bile homeostasis in Giardia-infected mice contributes to metabolic dysregulation and growth impairment. Sci. Transl. Med. 12, eaay7019 5. Ebneter, J.A. et al. (2016) Cyst-wall-protein-1 is fundamental for Golgi-like organelle neogenesis and cyst-wall biosynthesis in Giardia lamblia. Nat. Commun. 7, 13859 6. Jex, A.R. et al. (2020) Recent advances in functional research in Giardia intestinalis. Adv. Parasitol. 107, 97–137 7. Holthaus, D. et al. (2021) Dissection of barrier dysfunction in organoid-derived human intestinal epithelia induced by Giardia duodenalis. Gastroenterology Published online November 22, 2021. https://doi.org/10.1053/j.gastro.2021.11.022 8. Xu, F. et al. (2020) A chromosome-scale reference genome for Giardia intestinalis WB. Sci. Data 7, 38 9. McInally, S.G. et al. (2019) Robust and stable transcriptional repression in Giardia using CRISPRi. Mol. Biol. Cell 30, 119–130 10. Horáčková, V. et al. (2021) Cas9-mediated gene disruption in tetraploid Giardia intestinalis. bioRxiv Published online May 8, 2021. https://doi.org/10.1101/2021.04.21.440745 Trends in Parasitology | Parasite of the Month 606 Trends in Parasitology, July 2022, Vol. 38, No. 7 © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1016/j.pt.2022.01.001