Andrabi Syed Bilal Ahmad, Tahara Michiru, Matsubara Ryuma, Toyama Tomoko, Aonuma Hiroka, Sakakibara Hitoshi, Suematsu Makoto, Tanabe Kazuyuki, Nozaki Tomoyoshi, Nagamune Kisaburo
Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan; School of Medicine, Keio University, Tokyo, Japan.
Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
Parasitol Int. 2018 Feb;67(1):47-58. doi: 10.1016/j.parint.2017.03.003. Epub 2017 Mar 23.
Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression. Immunofluorescence microscopy and quantitative PCR analysis showed that t-zeatin increased the genome-copy number of apicoplast, which are non-photosynthetic plastid, in the parasite, while thidiazuron led to their disappearance. Thidiazuron inhibited growth of T. gondii and Plasmodium falciparum, a human malaria parasite, suggesting that thidiazuron has therapeutic potential as an inhibitor of apicomplexan parasites.
细胞分裂素是一类植物激素，参与细胞增殖、细胞周期进程以及细胞和质体发育的调控。在此，我们发现顶复门寄生虫刚地弓形虫和伯氏疟原虫（分别为一种机会性人类病原体和一种啮齿动物疟原虫）通过一条与植物中相似的生物合成途径产生细胞分裂素。细胞分裂素通过介导细胞周期蛋白基因TgCYC4的表达来调控刚地弓形虫的生长和细胞周期进程。细胞分裂素的一种天然形式，反式玉米素（t - 玉米素），上调了这种细胞周期蛋白的表达，而一种合成细胞分裂素，噻苯隆，则下调了其表达。免疫荧光显微镜和定量PCR分析表明，t - 玉米素增加了寄生虫中非光合质体——顶质体的基因组拷贝数，而噻苯隆导致其消失。噻苯隆抑制了刚地弓形虫和人类疟原虫恶性疟原虫的生长，这表明噻苯隆作为一种顶复门寄生虫抑制剂具有治疗潜力。
