Encystation of Giardia intestinalis—a Journey from the Duodenum to the Colon

Einarsson, Elin; Svärd, Staffan G.

doi:10.1007/s40475-015-0048-9

Cited by 7 publications

(9 citation statements)

References 75 publications

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“…Once G. lamblia leaves the host’s upper intestine, an increase in pH triggers encystation, leading to the stage differentiation of trophozoites to cysts ( 4 , 5 ). This dormant form of the parasite features a protective wall which enables it to survive in the environment ( 6 ). Regulation of the encystation process is essential for the timely production of viable cysts and, ultimately, for the success of the parasite-host colonization strategy.…”

Section: Introductionmentioning

confidence: 99%

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

Krtková

Thomas

Alas

et al. 2016

mBio

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Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia’s sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-RacCA) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-RacCA-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis.

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Section: Introductionmentioning

confidence: 99%

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

Krtková

Thomas

Alas

et al. 2016

mBio

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Section: Introductionmentioning

confidence: 99%

“…The encystation process, differentiation of trophozoites to cysts, is triggered by environmental changes, such as cholesterol deprivation, bile content, and pH [ 6 ]; however, the specific molecular mechanisms regulating cell differentiation remain unclear. Giardia encystation can be divided into an early and late phase [ 6 , 7 ]. During the early encystation phase, the adhesive disc is disassembled [ 8 ], the flagella are internalized, the cells round up, and the cyst wall formation starts [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Giardia encystation can be divided into an early and late phase [ 6 , 7 ]. During the early encystation phase, the adhesive disc is disassembled [ 8 ], the flagella are internalized, the cells round up, and the cyst wall formation starts [ 6 ]. In addition, the formation of Encystation Specific Vesicles (ESVs) occurs, and ESVs transport the three major cyst wall proteins (CWPs 1–3) to the cell surface [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…The CWPs make up most of the cyst wall, together with fibers of N-acetylgalactosamine, a sugar synthesized by enzymes, which are induced early in the encystation process [ 10 ]. In late encystation, division of the two nuclei occurs, DNA is replicated, and the maturation of the cyst wall is completed [ 6 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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A Detailed Gene Expression Map of Giardia Encystation

Rojas-López

Krakovka

Einarsson

et al. 2021

Genes

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Giardia intestinalis is an intestinal protozoan parasite that causes diarrheal infections worldwide. A key process to sustain its chain of transmission is the formation of infectious cysts in the encystation process. We combined deep RNAseq of a broad range of encystation timepoints to produce a high-resolution gene expression map of Giardia encystation. This detailed transcriptomic map of encystation confirmed a gradual change of gene expression along the time course of encystation, showing the most significant gene expression changes during late encystation. Few genes are differentially expressed early in encystation, but the major cyst wall proteins CWP-1 and -2 are highly up-regulated already after 3.5 h encystation. Several transcription factors are sequentially up-regulated throughout the process, but many up-regulated genes at 7, 10, and 14 h post-induction of encystation have binding sites in the upstream regions for the Myb2 transcription factor, suggesting that Myb2 is a master regulator of encystation. We observed major changes in gene expression of several meiotic-related genes from 10.5 h of encystation to the cyst stage, and at 17.5 h encystation, there are changes in many different metabolic pathways and protein synthesis. Late encystation, 21 h to cysts, show extensive gene expression changes, most of all in VSP and HCMP genes, which are involved in antigenic variation, and genes involved in chromatin modifications. This high-resolution gene expression map of Giardia encystation will be an important tool in further studies of this important differentiation process.

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Giardia and giardiasis

Ma’ayeh,

Svärd

2024

Molecular Medical Microbiology

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Encystation of Giardia intestinalis—a Journey from the Duodenum to the Colon

Cited by 7 publications

References 75 publications

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

A Detailed Gene Expression Map of Giardia Encystation

Giardia and giardiasis

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