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

Overview of attention for article published in BMC Biology, August 2017
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Title
Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development
Published in
BMC Biology, August 2017
DOI 10.1186/s12915-017-0406-2
Pubmed ID
Authors

Sujaan Das, Leandro Lemgruber, Chwen L. Tay, Jake Baum, Markus Meissner

Abstract

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. 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. 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.

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Geographical breakdown

Country Count As %
Unknown 84 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 27%
Researcher 13 15%
Student > Master 12 14%
Student > Bachelor 10 12%
Student > Doctoral Student 2 2%
Other 6 7%
Unknown 18 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 26 31%
Agricultural and Biological Sciences 18 21%
Immunology and Microbiology 7 8%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Engineering 2 2%
Other 8 10%
Unknown 19 23%