Gliding motility of Plasmodium merozoites

Abstract

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways.

Biophysical Tools and Concepts Enable Understanding of Asexual Blood Stage Malaria

“…Recent imaging of CRISPR Cas9 engineered parasite lines with fluorescent tags ( Lee et al., 2019 ), has boosted the study of specific ligand-receptor interactions at the molecular level. This has permitted the localisation of apical ligands that take part in the invasion ( Treeck et al., 2009 ), and showed that the invasion proceeds with the wider end of the merozoite leading, rather than the narrower pointed end, highlighting a remarkable motion of the merozoite that until now was mostly overlooked ( Yahata et al., 2021 ). Moreover, machine learning algorithms for image recognition have been employed to automatically detect infected cells and their stage ( Davidson et al., 2021 ).…”

The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites

“…CLAMP may also participate in the gliding motility of merozoites, which has recently emerged as an important precursor step during invasion of erythrocytes (Yahata et al, 2021). While TRAP is not expressed in merozoites and, unlike CLAMP, is dispensable for Plasmodium blood stage growth, merozoites express two members of the TRAP protein family, the merozoite thrombospondin-related anonymous protein (MTRAP) and the Plasmodium thrombospondin-related apical membrane protein (PTRAMP) (Baum et al, 2006; Morahan et al, 2009; Thompson et al, 2004).…”

“…CLAMP may also participate in the gliding motility of merozoites, which has recently emerged as an important precursor step during invasion of erythrocytes (Yahata et al, 2021).…”

The sulfonylpiperazine MMV020291 prevents red blood cell invasion by the malaria parasitePlasmodium falciparumthrough interference with actin-1/profilin dynamics

“…Additionally, the requirements for PfACT1 sequestering and subsequent turnover of F-actin may vary dependent on the process at hand. This can be realised by the varying speeds in motility in different stages of parasites; ookinetes move at 5 µm/min (Kan et al, 2014; Vlachou et al, 2006; Vlachou et al, 2004), merozoites are the next fastest at 36 µm/min (Yahata et al, 2021), whilst the fastest are sporozoites which can reach speeds of 60-120 µm/min (Hopp et al, 2015; Ripp et al, 2021).…”