The Structural and Molecular Underpinnings of Gametogenesis in Toxoplasma gondii

Abstract

Toxoplasma gondii is a widely prevalent protozoan parasite member of the phylum Apicomplexa. It causes disease in humans with clinical outcomes ranging from an asymptomatic manifestation to eye disease to reproductive failure and neurological symptoms. In farm animals, and particularly in sheep, toxoplasmosis costs the industry millions by profoundly affecting their reproductive potential. As do all the parasites in the phylum, T. gondii parasites go through sexual and asexual replication in the context of an heteroxenic life cycle involving members of the Felidae family and any warm-blooded vertebrate as definitive and intermediate hosts, respectively. During sexual replication, merozoites differentiate into female and male gametes; their combination gives rise to a zygotes which evolve into sporozoites that encyst and are shed in cat’s feces as environmentally resistant oocysts. During zygote formation T. gondii parasites are diploid providing the parasite with a window of opportunity for genetic admixture making this a key step in the generation of genetic diversity. In addition, oocyst formation and shedding are central to dissemination and environmental contamination with infectious parasite forms. In this minireview we summarize the current state of the art on the process of gametogenesis. We discuss the unique structures of macro and microgametes, an insight acquired through classical techniques, as well as the more recently attained molecular understanding of the routes leading up to these life forms by in vitro and in vivo systems. We pose a number of unanswered questions and discuss these in the context of the latest findings on molecular cues mediating stage switching, and the implication for the field of newly available in vitro tools.

The pathogenicity and virulence of Toxoplasma gondii

“…Macro- and microgametes are not equilibrated in numbers, and the rate of macrogamete fertilization is unknown. However, T. gondii has clearly managed to achieve maximum oocyst output, with hundreds of millions of them potentially being shed by a single felid [ 100 ]. Many questions still remain regarding these understudied stages [ 100 , 101 ].…”

Sexual Development in Non-Human Parasitic Apicomplexa: Just Biology or Targets for Control?

“…However, the two suborders Adeleorina and Eimeriorina differ greatly in their life cycles; Adeleorina develop via syzygy while Eimeriorina produce independent gametes. Of the many genera and species of the order, the sexual development has been studied in only several, including the model species T. gondii [56][57][58], certain species of the genus Eimeria [25,[59][60][61], and recently, Cystoisospora suis [53]. Sexual development of T. gondii occurs exclusively in the feline intestine [62], while Eimeria species can display distinct host and tissue tropisms, such as small and large intestines, stomach, the gallbladder or bile ducts, liver or gonads [63][64][65][66], but in most species, gamonts are formed in the intestinal lumen of the definitive host after merogony is completed, and the final generation of merozoites is considered to be sexually committed [67].…”

Structural and Functional Insights into the Microtubule Organizing Centers of <em>Toxoplasma gondii</em> and <em>Plasmodium spp</em>.

“…This expression pattern could reflect the involvement of the putative TgCen4 in BB biology. BBs may be either "recycled" or de novo assembled in male gametes of T. gondii (Tomasina & Francia, 2020). It is plausible that either of these processes requires use of a different/specialized protein set than those found in asexual centrosomes.…”

“…T. gondii microgametes, on the other hand, display two flagella, and the structure of their originating BB remains debatable (Francia et al, 2015;Tomasina & Francia, 2020).…”

“…Partly owed to the life stage's experimental inaccessibility in the cat's gut, the route of BB biogenesis in the T. gondii male gametes is poorly understood. However, new technical breakthroughs allowing microgamete formation in vitro will likely expedite our understanding of the process in the coming years (Farhat et al, 2020;Martorelli Di Genova et al, 2019;Tomasina & Francia, 2020).…”