Global Lysine Crotonylation and 2-Hydroxyisobutyrylation in Phenotypically Different Toxoplasma gondii Parasites

Abstract

<i>Toxoplasma gondii</i> is a unicellular protozoan parasite of the phylum Apicomplexa. The parasite repeatedly goes through a cycle of invasion, division and induction of host cell rupture, which is an obligatory process for proliferation inside warm-blooded animals. It is known that the biology of the parasite is controlled by a variety of mechanisms ranging from genomic to epigenetic to transcriptional regulation. In this study, we investigated the global protein posttranslational lysine crotonylation and 2-hydroxyisobutyrylation of two <i>T. gondii</i> strains, RH and ME49, which represent distinct phenotypes for proliferation and pathogenicity in the host. Proteins with differential expression and modification patterns associated with parasite phenotypes were identified. Many proteins in <i>T. gondii</i> were crotonylated and 2-hydroxyisobutyrylated, and they were localized in diverse subcellular compartments involved in a wide variety of cellular functions such as motility, host invasion, metabolism and epigenetic gene regulation. These findings suggest that lysine crotonylation and 2-hydroxyisobutyrylation are ubiquitous throughout the <i>T. gondii</i> proteome, regulating critical functions of the modified proteins. These data provide a basis for identifying important proteins associated with parasite development and pathogenicity.