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. 2018 Nov 8;8:16581. doi: 10.1038/s41598-018-34964-w

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic representation of synchronisation of P. falciparum with DFMO. The sole target of DFMO, pfadometdc/odc is expressed from 12 hours post-infection (hpi, transcript levels traced in top panel, data from PlasmoDB.org), resulting in detectable levels of putrescine (measured at representative early and late trophozoite and schizont stages; bar graphs in top panel). This provides a broad treatment window of ring-stage parasites after infection until 12–16 hpi (grey block) and results in parasite synchronisation in early trophozoite stages (corresponding to parasites at 18–22 hpi). The synchronisation and life cycle halt can be reversed by the addition of the product of PfAdoMetDC/ODC, putrescine, optimally after 24 h of DFMO pressure, resulting in parasites re-initiating life cycle development as normal. Samples taken at various time points after re-initiation (e.g. 3-hourly) provide data on processes involved in cell cycle control. Parasite drawings were modified from freely available images (https://smart.servier.com/), under a Creative Commons Attribution 3.0 Unported Licence.

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