Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation

Anahi V. Odell, Fanny Tran, Jenna E. Foderaro, Severine Poupart, Ravindra Pathak, Nicholas James Westwood, Gary E. Ward

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite’s life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.
Original languageEnglish
Article numbere0120331
JournalPLoS ONE
Volume10
Issue number3
DOIs
Publication statusPublished - 19 Mar 2015

Keywords

  • Yeast three-hybrid
  • Small-molecule
  • Target identification
  • Compound 2
  • Apicomplexa
  • Parasite
  • Toxoplasma gondii
  • Bradyzoite

Fingerprint

Dive into the research topics of 'Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation'. Together they form a unique fingerprint.

Cite this