Pantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii.

ABSTRACT

Coenzyme A (CoA) is an essential molecule acting in metabolism, post-translational modification, and regulation of gene expression. While all organisms synthesize CoA, many, including humans, are unable to produce its precursor, pantothenate. Intriguingly, like most plants, fungi and bacteria, parasites of the coccidian subgroup of Apicomplexa, including the human pathogen Toxoplasma gondii, possess all the enzymes required for de novo synthesis of pantothenate. Here, the importance of CoA and pantothenate biosynthesis for the acute and chronic stages of T. gondii infection is dissected through genetic, biochemical and metabolomic approaches, revealing that CoA synthesis is essential for T. gondii tachyzoites, due to the parasite's inability to salvage CoA or intermediates of the pathway. In contrast, pantothenate synthesis is only partially active in T. gondii tachyzoites, making the parasite reliant on its uptake. However, pantothenate synthesis is crucial for the establishment of chronic infection, offering a promising target for intervention against the persistent stage of T. gondii.