# Loss of TGME49_227100 (Glutaredoxin 5) Disrupts Oocyst Formation and Sporulation in Toxoplasma gondii

## TL;DR

This study shows that a protein called Grx5 is essential for Toxoplasma gondii to form and sporulate oocysts in cats, which could help in developing vaccines to block transmission.

## Contribution

The study identifies Grx5 as a key regulator of oocyst formation and sporulation in T. gondii.

## Key findings

- Grx5 deletion reduced oocyst production in cats by about 70%.
- Oocysts from Grx5-knockout parasites had a 50% lower sporulation rate.
- Grx5 is crucial for the feline host and environmental sporulation stages.

## Abstract

Oocysts of Toxoplasma gondii exhibit remarkable resistance to environmental stressors and most conventional disinfectants. Despite its ability to infect a wide variety of host species, sexual reproduction and oocyst formation occur exclusively within felid definitive hosts. Despite the epidemiological significance of oocyst-mediated transmission, the molecular mechanisms governing oocyst production and sporulation remain incompletely understood. Glutaredoxin, serving as a central regulator of cellular redox homeostasis and multiple vital cellular processes in cells, is a potential regulator for oocyst sporulation. Here, we investigated the role of TGME49_227100 (glutaredoxin 5, Grx5) in the T. gondii Pru strain-a type II strain capable of oocyst formation, with a particular focus on its functions during oocyst formation and sporulation. We found that Grx5-knockout tachyzoites exhibited no defects in growth or virulence. Neither in vitro nor in vivo tachyzoite-to-bradyzoite differentiation was affected compared to wild-type parasites. Notably, Grx5 deletion significantly reduced oocyst production in cats by approximately 70%. Additionally, the collected oocysts showed a 50% decrease in sporulation rate. These results indicate that Grx5 plays a predominant role within feline host and the external environmental stage of sporulation, which of these is likely to provide a crucial molecular target for developing a transmission-blocking vaccine.