Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development

BMC Biology

Research Article

Chwen L. Tay¹  Jake Baum¹  Leandro Lemgruber²  Sujaan Das²  Markus Meissner³ 

[1] Department of Life Sciences, Imperial College London, South Kensington, SW7 2AZ, London, UK;Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, G12 8TA, Glasgow, UK;Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, G12 8TA, Glasgow, UK;Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany;

关键词: Actin;    Cytoskeleton;    Invasion;    Apicoplast;    Cytokinesis;    Egress;    Merozoite;    Apicomplexa;    Malaria;    Plasmodium;    Plasmodium falciparum;    Actomyosin;    Conditional gene disruption;   

DOI  :  10.1186/s12915-017-0406-2

 received in 2017-06-21, accepted in 2017-07-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo characterisation during invasion is lacking.ResultsHere we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum blood-stage development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion.ConclusionsThis study provides important mechanistic insights into the definitive essential functions of PfACT1 in P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins, could also form the basis for the development of novel therapeutics against apicomplexans.

【 授权许可】

CC BY   
© Meissner et al. 2017