Preparing for Transmission: Gene Regulation in Plasmodium Sporozoites

Abstract

Plasmodium sporozoites are transmitted to mammals by anopheline mosquitoes and first infect the liver, where they transform into replicative exoerythrocytic forms, which subsequently release thousands of merozoites that invade erythrocytes and initiate the malaria disease. In some species, sporozoites can transform into dormant hypnozoites in the liver, which cause malaria relapses upon reactivation. Transmission from the insect vector to a mammalian host is a critical step of the parasite life cycle, and requires tightly regulated gene expression. Sporozoites are formed inside oocysts in the mosquito midgut and become fully infectious after colonization of the insect salivary glands, where they remain quiescent until transmission. Parasite maturation into infectious sporozoites is associated with reprogramming of the sporozoite transcriptome and proteome, which depends on multiple layers of transcriptional and post-transcriptional regulatory mechanisms. An emerging scheme is that gene expression in Plasmodium sporozoites is controlled by alternating waves of transcription activity and translational repression, which shape the parasite RNA and protein repertoires for successful transition from the mosquito vector to the mammalian host.

Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector

“…We found that a number of transcripts, including those for DHHC10, NTH, CPW-WPC family proteins, and LAP6 were downregulated in Pfarid – parasites. This might be indirectly driven by the observed downregulation of Pf HMGB2 in Pfarid – parasites, a member of the high mobility group box (HMGB) family, which in other organisms actively participates in chromatin remodeling by increasing nucleosome sliding and accessibility of the chromatin ( 71 ). Previous studies have implicated Py HMGB2 in regulating expression of the orthologous genes in P. yoelii ( 50 ).…”

Single-cell RNA sequencing ofPlasmodiumvivax sporozoites reveals stage- and species-specific transcriptomic signatures

“…These findings likely recapitulate the transcription changes occurring as the sporozoite transitions from a recently invaded salivary gland sporozoite to a mature one. Translational repression of mRNA is one molecular mechanism sporozoites use to ensure timely production of proteins upon entering its host (reviewed in (Briquet et al, 2021; Schäfer et al, 2021)). Our observation of the low number of UMIs and genes detected per cell, which corresponds with other assessments of Plasmodium sporozoites at single-cell resolution (Bogale et al, 2021; Howick et al, 2019; Real et al, 2021; Ruberto et al, 2021), suggests that transcriptional repression may also play a role in the sporozoites’ preparation for host invasion.…”

Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures

“…These findings likely recapitulate the transcriptional changes occurring as the sporozoite transitions from a recently invaded salivary gland sporozoite to a mature one. Translational repression of mRNA is one molecular mechanism sporozoites use to ensure timely production of proteins upon entering its host (reviewed in [54,55]). Our observation of the low number of UMIs and genes detected per cell, which corresponds with other assessments of Plasmodium sporozoites at single-cell resolution [22][23][24][25], suggests that transcriptional repression may also play a role in the sporozoites' preparation for host invasion.…”