TgATAT-mediated α-tubulin acetylation is required for division of the protozoan parasite Toxoplasma gondii

Joseph M. Varberg, Leah R. Padgett, Gustavo Arrizabalaga, William J. Sullivan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Toxoplasma gondii is a widespread protozoan parasite that causes potentially life-threatening opportunistic disease. New inhibitors of parasite replication are urgently needed, as the current antifolate treatment is also toxic to patients. Microtubules are essential cytoskeletal components that have been selectively targeted in microbial pathogens; further study of tubulin in Toxoplasma may reveal novel therapeutic opportunities. It has been noted that α-tubulin acetylation at lysine 40 (K40) is enriched during daughter parasite formation, but the impact of this modification on Toxoplasma division and the enzyme mediating its delivery have not been identified. We performed mutational analyses to provide evidence that K40 acetylation stabilizes Toxoplasma microtubules and is required for parasite replication. We also show that an unusual Toxoplasma homologue of α-tubulin acetyltransferase (TgATAT) is expressed in a cell cycle-regulated manner and that its expression peaks during division. Disruption of TgATAT with CRISPR/Cas9 ablates K40 acetylation and induces replication defects; parasites appear to initiate mitosis yet exhibit incomplete or improper nuclear division. Together, these findings establish the importance of tubulin acetylation, exposing a new vulnerability in Toxoplasma that could be pharmacologically targeted.

Original languageEnglish (US)
Article numbere00088-15
JournalmSphere
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Acetyltransferase
  • Cytoskeleton
  • Endodyogeny
  • Lysine acetylation
  • Mec-17
  • Microtubules

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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