An Ancient Protein Phosphatase, SHLP1, Is Critical to Microneme Development in Plasmodium Ookinetes and Parasite Transmission

Summary

Signaling pathways controlled by reversible protein phosphorylation (catalyzed by kinases and phosphatases) in the malaria parasite Plasmodium are of great interest, for both increased understanding of parasite biology and identification of novel drug targets. Here, we report a functional analysis in Plasmodium of an ancient bacterial Shewanella-like protein phosphatase (SHLP1) found only in bacteria, fungi, protists, and plants. SHLP1 is abundant in asexual blood stages and expressed at all stages of the parasite life cycle. shlp1 deletion results in a reduction in ookinete (zygote) development, microneme formation, and complete ablation of oocyst formation, thereby blocking parasite transmission. This defect is carried by the female gamete and can be rescued by direct injection of mutant ookinetes into the mosquito hemocoel, where oocysts develop. This study emphasizes the varied functions of SHLP1 in Plasmodium ookinete biology and suggests that it could be a novel drug target for blocking parasite transmission.

Abstract

Graphical Abstract

Highlights

► SHLP1 has phosphatase activity insensitive to phosphoprotein phosphatase inhibitors ► SHLP1 deletion results in reduced ookinete and microneme development ► SHLP1 is contributed by the female gamete ► SHLP1 deletion results in oocyst ablation and is critical for parasite transmission

Abstract

Reversible protein phosphorylation (catalyzed by protein kinases and phosphatases) in the malaria parasite Plasmodium is of great interest. Here, Tewari and colleagues report the first functional analysis of a Shewanella-like protein phosphatase (SHLP1) in rodent Plasmodium. SHLP1 is an enzyme that was reported previously only in bacteria, fungi, protists, and plants. Deletion of the gene results in reduced development of zygotes (ookinetes) and disruption of organelles (micronemes) associated with invasion into the mosquito gut, thus resulting in complete ablation of parasite transmission.