Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum
File(s)
Published version
OA Location
Author(s)
Blake, Thomas
Haase, Silvia
Baum, Jacob
Type
Journal Article
Abstract
All symptoms of malaria disease are associated with the asexual blood stages of development, involving cycles of red blood cell (RBC) invasion and egress by the Plasmodium spp. merozoite. Merozoite invasion is rapid and is actively powered by a parasite actomyosin motor. The current accepted model for actomyosin force generation envisages arrays of parasite myosins, pushing against short actin filaments connected to the external milieu that drive the merozoite forwards into the RBC. In Plasmodium falciparum, the most virulent human malaria species, Myosin A (PfMyoA) is critical for parasite replication. However, the precise function of PfMyoA in invasion, its regulation, the role of other myosins and overall energetics of invasion remain unclear. Here, we developed a conditional mutagenesis strategy combined with live video microscopy to probe PfMyoA function and that of the auxiliary motor PfMyoB in invasion. By imaging conditional mutants with increasing defects in force production, based on disruption to a key PfMyoA phospho-regulation site, the absence of the PfMyoA essential light chain, or complete motor absence, we define three distinct stages of incomplete RBC invasion. These three defects reveal three energetic barriers to successful entry: RBC deformation (pre-entry), mid-invasion initiation, and completion of internalisation, each requiring an active parasite motor. In defining distinct energetic barriers to invasion, these data illuminate the mechanical challenges faced in this remarkable process of protozoan parasitism, highlighting distinct myosin functions and identifying potential targets for preventing malaria pathogenesis.
Date Issued
2020-10-26
Date Acceptance
2020-09-28
Citation
PLoS Pathogens, 2020, 16 (10)
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
16
Issue
10
Copyright Statement
© 2020 Blake et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
Human Frontier Science Program
Grant Number
100993/Z/13/Z
100993/Z/13/Z
109007/Z/15/Z
RGY0066/2016
Subjects
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Virology
Publication Status
Published
Article Number
ARTN e1009007
Date Publish Online
2020-10-26