Plasmodium falciparum formins are essential for invasion and sexual stage development

Author:

Collier Sophie,Pietsch EmmaORCID,Dans Madeline,Ling DawsonORCID,Tavella Tatyana A.,Lopaticki Sash,Marapana Danushka S.,Shibu Mohini A.,Andrew Dean,Tiash Snigdha,McMillan Paul J.ORCID,Gilson PaulORCID,Tilley LeannORCID,Dixon Matthew W. A.ORCID

Abstract

AbstractThe malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including intracellular trafficking, gene regulation, parasite motility and invasion. In this work we assign functions to the Plasmodium falciparum formins 1 and 2 (FRM1 and FRM2) proteins in asexual and sexual blood stage development. We show that FRM1 is essential for merozoite invasion and FRM2 is required for efficient cell division. We also observed divergent functions for FRM1 and FRM2 in gametocyte development. Conditional deletion of FRM1 leads to a delay in gametocyte stage progression. We show that FRM2 controls the actin and microtubule cytoskeletons in developing gametocytes, with premature removal of the protein resulting in a loss of transmissible stage V gametocytes. Lastly, we show that targeting formin proteins with the small molecule inhibitor of formin homology domain 2 (SMIFH2) leads to a multistage block in asexual and sexual stage parasite development.

Funder

Department of Health | National Health and Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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