TY - JOUR
T1 - Plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites
AU - Andrabi, Syed Bilal Ahmad
AU - Tahara, Michiru
AU - Matsubara, Ryuma
AU - Toyama, Tomoko
AU - Aonuma, Hiroka
AU - Sakakibara, Hitoshi
AU - Suematsu, Makoto
AU - Tanabe, Kazuyuki
AU - Nozaki, Tomoyoshi
AU - Nagamune, Kisaburo
N1 - Funding Information:
This work was supported in part by Grants-in-Aids for Scientific Research 21590460 , 24390103 , and 15H04726 , and for Scientific Research on Innovative Areas 23117007 from the Ministry of Education, Culture, Sports, Science and Technology, Japan . This work was also supported by the Program for the Promotion to Improve Independent Research Environments for Young Scientists by Japan Science and Technology Agency , a grant for research on emerging and re-emerging infectious diseases from the Ministry of Health, Labor and Welfare of Japan H23-Shinkosaiko-ippan-014 , a grant for research to promote the development of anti-AIDS pharmaceuticals from the Japan Health Sciences Foundation KHA1101 , the Emerging/Re-emerging Infectious Diseases Project of Japan from Japan Agency for Medical Research and development (AMED), the Naito Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Sumitomo Foundation, the Takeda Science Foundation, and the Uehara Memorial Foundation. The authors declare no conflicts of interest.
Publisher Copyright:
© 2017 The Authors
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - Cytokinins
KW - Plant hormones
KW - Plasmodium berghei
KW - Thidiazuron
KW - Toxoplasma gondii
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U2 - 10.1016/j.parint.2017.03.003
DO - 10.1016/j.parint.2017.03.003
M3 - Article
C2 - 28344153
AN - SCOPUS:85017426173
VL - 67
SP - 47
EP - 58
JO - Parasitology International
JF - Parasitology International
SN - 1383-5769
IS - 1
ER -