Checks and balances? DNA replication and the cell cycle in Plasmodium

Matthews, Holly; Duffy, Craig W.; Merrick, Catherine J.

Abstract

It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that may prove crucial for our efforts to control the disease. Phenotypic screens have partially filled the void in the antimalarial drug market, but as compound libraries eventually become exhausted, new medicines will only come from directed drug development based on a better understanding of fundamental parasite biology. This review focusses on the unusual cell cycles of Plasmodium, which may present a rich source of novel drug targets as well as a topic of fundamental biological interest. Plasmodium does not grow by conventional binary fission, but rather by several syncytial modes of replication including schizogony and sporogony. Here, we collate what is known about the various cell cycle events and their regulators throughout the Plasmodium life-cycle, highlighting the differences between Plasmodium, model organisms and other apicomplexan parasites and identifying areas where further study is required. The possibility of DNA replication and the cell cycle as a drug target is also explored. Finally the use of existing tools, emerging technologies, their limitations and future directions to elucidate the peculiarities of the Plasmodium cell cycle are discussed.

• Journal Article Type: Review
• Online Publication Date: Mar 27, 2018
• Publication Date: 2018-12
• Deposit Date: May 23, 2025
• Publicly Available Date: May 29, 2025
• Journal: Parasites & Vectors
• Print ISSN: 1756-3305
• Electronic ISSN: 1756-3305
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Article Number: 216
• DOI: https://doi.org/10.1186/s13071-018-2800-1
• Additional Information: Received: 3 January 2018; Accepted: 19 March 2018; First Online: 27 March 2018; : Not applicable.; : Not applicable.; : The authors declare that they have no competing interests.; : Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.