Role of amylopectin synthesis in Toxoplasma gondii and its implication in vaccine development against toxoplasmosis.

Congcong Lyu,Bang Shen,Lun Hou,Jichao Yang,Yanqin Zhou,Junlong Zhao,Xuke Yang

doi:10.1098/rsob.200384

Abstract

Toxoplasma gondii is a ubiquitous pathogen infecting one-third of the global population. A significant fraction of toxoplasmosis cases is caused by reactivation of existing chronic infections. The encysted bradyzoites during chronic infection accumulate high levels of amylopectin that is barely present in fast-replicating tachyzoites. However, the physiological significance of amylopectin is not fully understood. Here, we identified a starch synthase (SS) that is required for amylopectin synthesis in T. gondii. Genetic ablation of SS abolished amylopectin production, reduced tachyzoite proliferation, and impaired the recrudescence of bradyzoites to tachyzoites. Disruption of the parasite Ca2+-dependent protein kinase 2 (CDPK2) was previously shown to cause massive amylopectin accumulation and bradyzoite death. Therefore, the Δcdpk2 mutant is thought to be a vaccine candidate. Notably, deleting SS in a Δcdpk2 mutant completely abolished starch accrual and restored cyst formation as well as virulence in mice. Together these results suggest that regulated amylopectin production is critical for the optimal growth, development and virulence of Toxoplasma. Not least, our data underscore a potential drawback of the Δcdpk2 mutant as a vaccine candidate as it may regain full virulence by mutating amylopectin synthesis genes like SS.

Highlights

Toxoplasma gondii is an obligate intracellular parasite of the protozoan phylum Apicomplexa that comprise many parasitic pathogens of medical and veterinary importance, such as Plasmodium and Eimeria species
Our work focused on a starch synthase (SS) that we show is involved in amylopectin biosynthesis in T. gondii
We first searched for the enzymatic pathways that may catalyse amylopectin synthesis and degradation in T. gondii

Summary

Introduction

Toxoplasma gondii is an obligate intracellular parasite of the protozoan phylum Apicomplexa that comprise many parasitic pathogens of medical and veterinary importance, such as Plasmodium and Eimeria species. Infections by Toxoplasma are highly prevalent in humans and animals [1,2]. Oocysts shed by cats in the environment serve as a major source of infection to new hosts [5]. Toxoplasma can be transmitted between intermediate hosts that include many warm-blooded animals [6,7,8]. Toxoplasma gondii exists in two asexual forms in its intermediate hosts. A fast-replicating tachyzoite form that underlies acute infection and associated clinical symptoms, and a slow-growing bradyzoite form that causes persistent, usually life-long, chronic infection [4,10]. Depending on the environmental cues, tachyzoites and bradyzoites can interconvert, which is crucial for the pathogenesis and transmission of T. gondii [11]. The molecular mechanisms that govern such conversions remain largely elusive

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Conclusion