Intestinal delta-6-desaturase activity determines host range forToxoplasmasexual reproduction

Many eukaryotic microbes have complex lifecycles that include both sexual and asexual phases with strict species-specificity. While the asexual cycle of the protistan parasiteToxoplasma gondiican occur in any warm-blooded mammal, the sexual cycle is restricted to the feline intestine¹. The molecular determinants that identify cats as the definitive host forT. gondiiare unknown. Here, we defined the mechanism of species specificity forT. gondiisexual development and break the species barrier to allow the sexual cycle to occur in mice. We determined thatT. gondiisexual development occurs when cultured feline intestinal epithelial cells are supplemented with linoleic acid. Felines are the only mammals that lack delta-6-desaturase activity in their intestines, which is required for linoleic acid metabolism, resulting in systemic excess of linoleic acid^{2, 3}. We found that inhibition of murine delta-6-desaturase and supplementation of their diet with linoleic acid allowedT. gondiisexual development in mice. This mechanism of species specificity is the first defined for a parasite sexual cycle. This work highlights how host diet and metabolism shape coevolution with microbes. The key to unlocking the species boundaries for other eukaryotic microbes may also rely on the lipid composition of their environments as we see increasing evidence for the importance of host lipid metabolism during parasitic lifecycles^{4, 5}. Pregnant women are advised against handling cat litter as maternal infection withT. gondiican be transmitted to the fetus with potentially lethal outcomes. Knowing the molecular components that create a conducive environment forT. gondiisexual reproduction will allow for development of therapeutics that prevent shedding ofT. gondiiparasites. Finally, given the current reliance on companion animals to studyT. gondiisexual development, this work will allow theT. gondiifield to use of alternative models in future studies.