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.
Bibliographical noteKAUST Repository Item: Exported on 2022-09-14
Acknowledged KAUST grant number(s): BAS/1/1020-01-01, OCRF-20146CRG4
Acknowledgements: ST acknowledges a LabEx ParaFrap postdoctoral fellowship and GL acknowledges ANR-11-LABX-0024 support and core funding from INSERM and the CNRS. AC received funding from Head of College Scholars List Scheme, College of Medical, Veterinary and Life Sciences, University of Glasgow for a summer project. AP acknowledges the financial support received from KAUST in form of OCRF-20146CRG4 and BAS/1/1020-01-01 grants. We thank members of the KAUST Bioscience Core Laboratory (BCL) to generate the raw sequence datasets. We thank.
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