Toxoplasma gondii Fatty Acid Elongases are Important for Virulence and Persistence

Toxoplasma gondii is an apicomplexan parasite which can infect a diverse range of warm-blooded host species. This promiscuous lifestyle requires metabolic flexibility yet our understanding of the metabolic pathways in this parasite remains incomplete. This gap includes the endoplasmic reticulum localised fatty acid elongation (FAE) pathway, which is responsible for synthesis of long (LCFA) and very long chain fatty acids (VLCFA), thus contributing to critical functions such as lipid storage and membrane biogenesis. Analyses of FAE in the commonly studied type I T. gondii strain revealed its contribution to the production of LCFA and VLCFA in vitro . However, the cystogenic type II T. gondii, which is responsible for most toxoplasmosis cases worldwide, was not studied. These type II parasites can readily differentiate between virulent and immune-evasive stages whereas type I cannot. This ability to readily transition between life stages, which are metabolically fundamentally different, prompts the question of whether the FAE pathway may play different roles in their distinct phenotype. Here we address this question, first confirming the role of the FAE enzymes, TgELO-A & B, in the production of LCFA and VLCFA in a type II T. gondii strain. Next, we demonstrated that their deletion leads to defects in replication and invasion when grown under lipid-restricted conditions. The mutants were further shown to be attenuated in mice as demonstrated by extended survival. Importantly, FAE enzyme deletion caused reduced brain cyst burdens. These findings highlight the importance of FAE for parasite survival under metabolic stress and in vivo .