Toxoplasma gondii DNA methyltransferases regulate parasitic energy metabolism

The intracellular protozoan Toxoplasma gondii results in serious diseases such as encephalitis, and retinochoroiditis in immunocompromised patients. The interconversion between tachyzoites and bradyzoites under the host's immune pressure results in the interchange of acute infection and chronic infection. We previously reported two functional DNA methyltransferases (DNMT) in Toxoplasma gondii named TgDNMTa and TgDNMTb. In this research, proteomics analysis for T. gondii tachyzoites of ME49 WT, dnmta knockout (ME49-∆Tgdnmta), and dnmtb knockout (ME49-∆Tgdnmtb) strains, revealed 362 significantly regulated proteins for ME49-∆Tgdnmta, and 219 for ME49-∆Tgdnmtb, compared with the proteins of ME49 WT. TgDNMTa down regulated three glycolytic enzymes, one gluconeogenic enzyme and four pyruvate metabolic enzymes. Furthermore, TgDNMTb up regulated two proteins in the tricarboxylic acid (TCA) cycle. Glucose metabolic flux detection showed that TgDNMTa inhibited the glycolysis pathway, while TgDNMTb promoted the tricarboxylic acid (TCA) cycle so as to promote parasite's proliferation. These findings demonstrated that the functions of Toxoplasma gondii DNA methyltransferases extended beyond DNA methylation to the regulation of parasitic energy metabolism.