Location: Animal Parasitic Diseases Laboratory
Title: Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproductionAuthor
DI GENOVA, BRUNO - University Of Wisconsin | |
WISON, SARAH - University Of Wisconsin | |
Dubey, Jitender | |
KNOLL, LAURA - University Of Wisconsin |
Submitted to: PLoS Biology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 7/17/2019 Publication Date: 8/20/2019 Citation: Di Genova, B., Wison, S., Dubey, J.P., Knoll, L. 2019. Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction. PLoS Biology. 17(8):e3000364. https://doi.org/10.1371/journal.pbio.3000364. DOI: https://doi.org/10.1371/journal.pbio.3000364 Interpretive Summary: Most emerging infectious diseases in humans are zoonoses. Among these pathogens, the zoonotic protozoan parasite T. gondii is perhaps the most ubiquitous, having been identified in the tissues of a variety of animal hosts, including both mammalian and avian species. Humans become infected by eating undercooked meat or by ingesting food and water contaminated with the resistant stage of the parasite (called oocysts). Of all warm- blooded hosts infected worldwide only cats can excrete oocysts. The reasons for this dependency to complete the sexual phase of the parasite and oocyst formation were unknown until now.Cats are arachidonic acid auxotrophs and are the only mammals that lack delta-6-desaturase activity in their intestines. The authors found that inhibition of murine delta-6-desaturase and diet supplementation with linoleic acid broke the species barrier and allowed Toxoplasma sexual development. This mechanism of species specificity is the first defined for a parasite sexual cycle. The results will be of interest to biologists, parasitologists, veterinarian, public health workers and scientists in general. Technical Abstract: Most Protista and helminth parasites have complex lifecycles with strict species specificity for their definitive host, but the molecular determinants that define that selectivity are unknown. The sexual cycle of the parasite Toxoplasma gondii is restricted to the feline intestine. We determined that Toxoplasma sexual development is prolific when feline intestinal organoids are supplemented with linoleic acid. After ingestion, linoleic acid is rapidly shunted into the arachidonic acid synthesis pathway by delta-6-desaturase. Cats are arachidonic acid auxotrophs and are the only mammals that lack delta-6-desaturase activity in their intestines. We found that inhibition of murine delta-6-desaturase and diet supplementation with linoleic acid broke the species barrier and allowed Toxoplasma sexual development in the mouse. This mechanism of species specificity is the first defined for a parasite sexual cycle. |