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

Das, S., Lemgruber, L., Tay, C. L., Baum, J. and Meissner, M. (2017) Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development. BMC Biology, 15(1), 70. (doi:10.1186/s12915-017-0406-2) (PMID:28810863) (PMCID:PMC5557482)

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Abstract

Background The 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. Results Here 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. Conclusions This 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Meissner, Professor Markus and Lemgruber Soares, Dr Leandro and Das, Dr Sujaan
Authors: Das, S., Lemgruber, L., Tay, C. L., Baum, J., and Meissner, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:BMC Biology
Publisher:BioMed Central
ISSN:1741-7007
ISSN (Online):1741-7007
Copyright Holders:Copyright © 2017 Meissner et al.
First Published:First published in BMC Biology 15(1):70
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
501601Systematic analysis of essential parasite genes linked to invasion of the host cell in Toxoplasma gondiiMarkus MeissnerWellcome Trust (WELLCOTR)087582/Z/08/ZIII - PARASITOLOGY