The antioxidant protein glutaredoxin 1 is essential for oxidative stress response and pathogenicity of Toxoplasma gondii

Li, Ting-Ting; Zhao, Dan-Yu; Liang, Qin-Li; Elsheikha, Hany M.; Wang, Meng; Sun, Li-Xiu; Zhang, Zhi-Wei; Chen, Xiao-Qing; Zhu, Xiang-Quan; Wang, Jin-Lei

Abstract

Glutaredoxins (Grxs) are ubiquitous antioxidant proteins involved in many molecular processes to protect cells against oxidative damage. Here, we study the roles of Grxs in the pathogenicity of Toxoplasma gondii. We show that Grxs are localized in the mitochondria (Grx1), cytoplasm (Grx2), and apicoplast (Grx3, Grx4), while Grx5 had an undetectable level of expression. We generated Δgrx1-5 mutants of T. gondii type I RH and type II Pru strains using CRISPR-Cas9 system. No significant differences in the infectivity were detected between four Δgrx (grx2-grx5) strains and their respective wild-type (WT) strains in vitro or in vivo. Additionally, no differences were detected in the production of reactive oxygen species, total antioxidant capacity, superoxide dismutase activity, and sensitivity to external oxidative stimuli. Interestingly, RHΔgrx1 or PruΔgrx1 exhibited significant differences in all the investigated aspects compared to the other grx2-grx5 mutant and WT strains. Transcriptome analysis suggests that deletion of grx1 altered the expression of genes involved in transport and metabolic pathways, signal transduction, translation, and obsolete oxidation-reduction process. The data

• Journal Article Type: Article
• Acceptance Date: Apr 7, 2023
• Online Publication Date: Apr 28, 2023
• Publication Date: 2023-06
• Deposit Date: Apr 29, 2023
• Journal: The FASEB Journal
• Print ISSN: 0892-6638
• Electronic ISSN: 1530-6860
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 37
• Issue: 6
• Article Number: e22932
• DOI: https://doi.org/10.1096/fj.202201275r
• Keywords: Genetics, Molecular Biology, Biochemistry, Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/20074379
• Publisher URL: https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202201275R