Differentiation‐associated surface antigen variation in the ancient eukaryote Giardia lamblia

  title={Differentiation‐associated surface antigen variation in the ancient eukaryote Giardia lamblia},
  author={Staffan G. Sv{\"a}rd and T C Meng and Michael L. Hetsko and J Michael McCaffery and Frances D. Gillin},
  journal={Molecular Microbiology},
Encystation of Giardia lamblia is required for survival outside the host, whereas excystation initiates infection. The dormant cyst was considered an adaptation to external survival and passage through the stomach. However, we found previously that trophozoites which had recovered after completion of the life cycle had switched their major variant surface protein (VSP), called TSA 417, but neither the timing nor the molecular mechanism of switching had been elucidated. Here we demonstrate that… 
Antigenic Variation in Giardia
Giardia lamblia trophozoites undergo surface antigenic variation where one member of a family of related proteins, variant specific surface proteins (VSPs), is expressed but periodically replaced by another, essential for the development of immunity, immune selection, and immune evasion as well as biological selection.
Proteomics of Secretory and Endocytic Organelles in Giardia lamblia
The first proteome of ESVs and PVs is defined using a novel strategy combining flow cytometry-based organelle sorting with in silico filtration of mass spectrometry data to provide further evidence for the formation of a cyst extracellular matrix with minimal complexity.
Antigenic variation in Giardia lamblia
The characteristics of this fascinating mechanism are summarized, conflicting information regarding the structure of VSPs as it relates to the host's immune response is analysed, and the major issues that need to be resolved to fully understand antigenic variation in this important pathogen are highlighted.
Antigenic Variation of the VSP Genes of Giardia Lamblia
Giardia undergoes surface antigenic variation in humans and animal model infections, a phenomenon that may account for both chronicity of infections and the relatively broad mammalian host specificity with genotypically identical organisms found in humans, cats, beavers, and other mammals.
Export of cyst wall material and Golgi organelle neogenesis in Giardia lamblia depend on endoplasmic reticulum exit sites
The data show how ERES domains remain conserved in G. lamblia despite elimination of steady‐state Golgi, and the fundamental eukaryotic principle of ERES to Golgi/Golgi‐like compartment correspondence holds true in differentiating Giardia presenting streamlined machinery for secretory organelle biogenesis and protein trafficking.
Export of cyst wall material and Golgi organelle neogenesis in Giardia lamblia depends on ER exit sites 1
The data show how ERES domains remain conserved in G. lamblia despite elimination of steady-state Golgi, and the fundamental eukaryotic principle of ERES to Golgi/Golgi-like compartment correspondence holds true in differentiating Giardia presenting streamlined machinery for secretory organelle biogenesis and protein trafficking.
Cell cycle and differentiation in Giardia Lamblia
This work developed for the first time a method of synchronizing Giardia for use to determine where the encystation restriction point is in the cell cycle, and used quantitative real-time PCR to determine the periodic cell cycle regulation of histones.
Surface antigenic variation in Giardia lamblia
  • T. Nash
  • Biology, Medicine
    Molecular microbiology
  • 2002
Giardia lamblia , a common intestinal dwelling protozoan and a cause of diarrhoea in humans and animals world‐wide, undergoes surface antigenic variation. The variant‐specific surface proteins (VSPs)
Mining the Giardia lamblia Genome for New Cyst Wall Proteins*
Five new LRR-containing proteins are identified, of which only one (CWP3) is up-regulated during encystation and incorporated into the cyst wall, demonstrating the power of genomics in combination with rigorous functional analyses to verify annotation.
The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution
The data presented here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.


Giardia lamblia: traffic of a trophozoite variant surface protein and a major cyst wall epitope during growth, encystation, and antigenic switching.
It is proposed that this may be the initiation of a stage in differentiation-driven antigenic switching of TSA 417, in which this antigen is no longer synthesized or exported to the plasmalemma, but is taken back inside the cell.
Cellular and transcriptional changes during excystation of Giardia lamblia in vitro.
Findings show that excystation of G. lamblia is a highly complex and active process and provide important insights into its cellular and molecular components.
Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei.
The data suggest that trypanosomes synthesize or activate a developmentally-regulated proteinase which degrades the glycoproteins at the surface, at the membrane lining the flagellar pocket, and/or in an early endocytic compartment.
Developmentally regulated transcripts and evidence of differential mRNA processing in Giardia lamblia.
Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei
This is the first demonstration of gene expression being regulated entirely at the level of transcription among the Kinetoplastida; all other protein-coding genes examined in these organisms are, at least partly, under posttranscriptional control.
Stage-specific mechanisms for activation and expression of variant surface glycoprotein genes in Trypanosoma brucei.
The African trypanosomes undergo extensive development as they proceed through their life cycle, producing a range of stages with distinct functions. In response to the somewhat treacherous,
Analysis of Trypanosoma brucei vsg expression site switching in vitro.
Antigenic switching of TSA 417, a trophozoite variable surface protein, following completion of the life cycle of Giardia lamblia
In vitro excystation of cysts derived in vitro or in vivo consistently produced TSA 417 nonexpressing trophozoite populations, suggesting that completion of the life cycle leads to antigenic switching.
Genetic controls for the expression of surface antigens in African trypanosomes.
This review discusses the available information concerning the genetic mechanisms that control the expression of VSG and procyclin during the life-cycle of the trypanosome and discusses the general organization of genes in long polycistronic transcription units.
Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy.
The distribution of immunogold-marked nascent metacyclics of a particular variable antigen type, as shown by quadrat analysis of a scanning electron micrograph montage of the infected salivary gland epithelium, conforms to a Poisson series, provides evidence that individual variant surface glycoprotein genes are stochastically activated and suggests that selective activation occurs after trypanosome division has ceased.