Malaria parasites differentially sense environmental elasticity during transmission.

Johanna Ripp,Nathalie Tisch,Friedrich Frischknecht,Carmen Ruiz De Almodovar,Rogerio Amino,Xanthoula Smyrnakou,Joana Tavares,Jessica Kehrer

doi:10.15252/emmm.202113933

Abstract

Transmission of malaria‐causing parasites to and by the mosquito relies on active parasite migration and constitutes bottlenecks in the Plasmodium life cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 h on soft substrates. In contrast, sporozoites evolved more short‐lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion to soft endothelial cells on their long way to the liver. Hence, the two migratory stages of Plasmodium evolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter.

Highlights

Plasmodium parasites need to invade host cells and migrate across tissues at different stages throughout their life cycle (Fig EV1A)
We show that ookinetes and sporozoites are able to move at fast speeds if confined between or within uncoated PA hydrogels
Tuning of these PA gels to elasticities as they occur on the natural substrates encountered by the parasites revealed intriguing differences between the motile behavior of ookinetes and sporozoites

Summary

Introduction

Plasmodium parasites need to invade host cells and migrate across tissues at different stages throughout their life cycle (Fig EV1A). The parasite forms developing inside the mosquito midgut after an infectious blood meal, the ookinetes, have to leave the blood meal and traverse the midgut epithelium to transform into oocysts at the basal membrane (Zieler & Dvorak, 2000; Vlachou et al, 2004; Kumar & Barillas-Mury, 2005; Kan et al, 2014). These sporozoites move inside the oocyst and egress (Klug & Frischknecht, 2017) They are transported within the mosquito circulatory system until they attach to and invade the salivary gland (Pimenta et al, 1994). Liver invasion is thought to be triggered by highly sulfated heparan sulfate proteoglycans which protrude through fenestrations of endothelial cells lining the liver sinusoids (Pradel et al, 2002; Coppi et al, 2007; Tavares et al, 2013)

Methods

Results

Conclusion