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Abstract
A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata, another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes including a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites.
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Details
1 Université Paris Descartes – Sorbonne Paris Cité, Laboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Cochin Institute, INSERM U1016, CNRS UMR8104, Paris, France (GRID:grid.462098.1) (ISNI:0000 0004 0643 431X); Freie Universität Berlin, Institute for Parasitology and Tropical Veterinary Medicine, Berlin, Germany (GRID:grid.14095.39) (ISNI:0000 0000 9116 4836)
2 Université Paris Descartes – Sorbonne Paris Cité, Laboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Cochin Institute, INSERM U1016, CNRS UMR8104, Paris, France (GRID:grid.462098.1) (ISNI:0000 0004 0643 431X)
3 Institut Cochin, Plateforme Génomique, Paris, France (GRID:grid.462098.1) (ISNI:0000 0004 0643 431X)
4 King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, BESE Division, Thuwal, Saudi Arabia (GRID:grid.45672.32) (ISNI:0000 0001 1926 5090)
5 University of Glasgow, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, Glasgow, UK (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X)
6 King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, BESE Division, Thuwal, Saudi Arabia (GRID:grid.45672.32) (ISNI:0000 0001 1926 5090); Hokkaido University, International Institute for Zoonosis Control, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691)