Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction

Upinder Singh; Jeremy L Brewer; John C Boothroyd

doi:10.1046/j.1365-2958.2002.02903.x

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Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction

Journal article

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Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction

Upinder Singh, Jeremy L Brewer and John C Boothroyd

Molecular microbiology, Vol.44(3), pp.721-733

05/2002

DOI: 10.1046/j.1365-2958.2002.02903.x

PMID: 11994153

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Abstract

Developmental switching in Toxoplasma gondii, from the virulent tachyzoite to the relatively quiescent bradyzoite stage, is responsible for disease propagation and reactivation. We have generated tachyzoite to bradyzoite differentiation (Tbd-) mutants in T. gondii and used these in combination with a cDNA microarray to identify developmental pathways in bradyzoite formation. Four independently generated Tbd- mutants were analysed and had defects in bradyzoite development in response to multiple bradyzoite-inducing conditions, a stable phenotype after in vivo passages and a markedly reduced brain cyst burden in a murine model of chronic infection. Transcriptional profiles of mutant and wild-type parasites, growing under bradyzoite conditions, revealed a hierarchy of developmentally regulated genes, including many bradyzoite-induced genes whose transcripts were reduced in all mutants. A set of non-developmentally regulated genes whose transcripts were less abundant in Tbd- mutants were also identified. These may represent genes that mediate downstream effects and/or whose expression is dependent on the same transcription factors as the bradyzoite-induced set. Using these data, we have generated a model of transcription regulation during bradyzoite development in T. gondii. Our approach shows the utility of this system as a model to study developmental biology in single-celled eukaryotes including protozoa and fungi.

Animals

Antiprotozoal Agents - pharmacology

Atovaquone

Cell Differentiation - genetics

Gene Expression Profiling

Gene Expression Regulation, Developmental

Genes, Protozoan

Genes, Reporter

Green Fluorescent Proteins

Luminescent Proteins - biosynthesis

Luminescent Proteins - genetics

Mice

Mutagenesis

Naphthoquinones - pharmacology

Oligonucleotide Array Sequence Analysis

Phenotype

Protozoan Proteins - biosynthesis

Protozoan Proteins - genetics

Recombinant Fusion Proteins - biosynthesis

Recombinant Fusion Proteins - genetics

Selection, Genetic

Toxoplasma - drug effects

Toxoplasma - genetics

Toxoplasma - growth & development

Toxoplasmosis, Animal - parasitology

Transcription, Genetic

Transcriptional Activation

Details

Title: Subtitle: Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction
Creators: Upinder Singh - Stanford Medicine
Jeremy L Brewer - Stanford Medicine
John C Boothroyd - Stanford Medicine
Resource Type: Journal article
Publication Details: Molecular microbiology, Vol.44(3), pp.721-733
DOI: 10.1046/j.1365-2958.2002.02903.x
PMID: 11994153
NLM abbreviation: Mol Microbiol
ISSN: 0950-382X
eISSN: 1365-2958
Grant note: K08 AI01453 / NIAID NIH HHS AI41014 / NIAID NIH HHS
Language: English
Date published: 05/2002
Academic Unit: Internal Medicine
Record Identifier: 9985244667002771

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