弓形虫DNA甲基转移酶调控寄生能量代谢的蛋白质组学研究

Abstract

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 Tg DNMTa and Tg DNMTb. In this research, proteomics analysis for T. gondii tachyzoites of ME49 WT, dnmta knockout (ME49-∆ Tg dnmta), and dnmtb knockout (ME49-∆ Tg dnmtb) strains, revealed 362 significantly regulated proteins for ME49-∆ Tg dnmta, and 219 for ME49-∆ Tg dnmtb, compared with the proteins of ME49 WT. Tg DNMTa down regulated three glycolytic enzymes, one gluconeogenic enzyme and four pyruvate metabolic enzymes. Furthermore, Tg DNMTb up regulated two proteins in the tricarboxylic acid (TCA) cycle. Glucose metabolic flux detection showed that Tg DNMTa inhibited the glycolysis pathway, while Tg DNMTb 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.