Toxoplasma gondii is a microbial parasite that infect humans and complete its full life cycle only in cats. New research published August 20 in the open-access journal PLOS Biology shows why: the sexual phase of the parasite's life cycle requires linoleic acid, a nutrient/lipid found at uniquely high levels in the felines, because cats lack a key enzyme for breaking it down. The finding, from by Bruno Martorelli Di Genova and Laura Knoll of the University of Wisconsin-Madison and colleagues, is likely to help in the development of treatments to reduce spread of the parasite from cats to their human companions. Also, presents an opportunity to avoid using cats for Toxoplasma research.
Toxoplasma can live asexually in any mammal, including humans. But it forms gametes (sexual cells) only in cats, a restriction that has long been recognized, but whose reason was not understood. The authors suspected something was missing when reproducing the infections in vitro and not observing sexual development. It is known that fungi require linoleic acid for sexual development. To test Toxoplasma's requirement for the same lipid, they generated cat intestinal organoids--three-dimensional "test tube" models that share several essential properties with actual intestines--and showed that linoleic acid was required for sexual reproduction of the parasite. Cats lack an enzyme called delta-6-desaturase, which catalyzes the conversion of linoleic acid to arachidonic acid, accounting for the peculiarly high levels of linoleic acid in the cat intestine, but not in other mammals. When the authors supplemented the diet of mice with linoleic acid, and added a specific inhibitor of the enzyme, Toxoplasma could complete the sexual phase of its life cycle in the mouse intestine.
Toxoplasma is the leading cause of foodborne illness in the US, according to CDC. The most common route of infection for human is by consumption of contaminated raw or undercooked meat. Cat litter, after 24-48 of being cleaned, can also a source of Toxoplasma infection. However, cats can only shed oocysts once in their life time. Pregnant women are urged to avoid eating raw or undercooked meat, as also avoiding cleaning the litterbox after 48 hours, to prevent Toxoplasma infection. Congenital toxoplasmosis can have potentially serious consequences for the unborn child. An improved understanding of the parasite life cycle stemming from this study may lead to production of vaccines that could inhibit Toxoplasma's sexual reproduction or the transmission of Toxoplasma to livestock.
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Citation: Martorelli Di Genova B, Wilson SK, Dubey JP, Knoll LJ (2019) Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction. PLoS Biol 17(8): e3000364. https:/
Funding: This research was supported by the National Institutes of Health (NIH) National Research Service Award T32 AI007414 (SKW), R01AI144016-01, 5R21AI1123289-02, and 5R03AI104697-02 (LJK) and the Morgridge Metabolism Interdisciplinary Fellowship from the Morgridge Institute for Research (BMDG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.