Genome-wide CRISPR screens for the identification of essential host factors for Toxoplasma gondii infection

Abstract text

Toxoplasma gondii is an apicomplexan parasite infecting virtually all warm-blooded animals, including birds. Roughly one fourth of the human population is chronically infected with this parasite. While mostly asymptomatic, chronic toxoplasmosis can exacerbate as a life-threatening acute condition in immunocompromised adults, such as people living with untreated AIDS and chemotherapy patients. From a veterinary point of view, Toxoplasma is also a parasite of significant economic burden, causing major losses in livestock production mainly due to abortion in small ruminants. Currently, none of the treatments available are sufficient to eliminate quiescent tissue cysts and eradicate the parasite from its host. Whilst to date most of the research on the molecular basis of the host-parasite interaction is focused on the parasite itself, little is known regarding the host factors that Toxoplasma requires for establishing infection. Notably, obligate intracellular parasites largely rely on the host cell, e.g. for the acquisition of essential metabolites and the release of toxic waste products. We are currently testing FACS-based genome-wide CRISPR/Cas9 knockout screens with the aim of identifying host factors that Toxoplasma gondii needs for intracellular development. Some of these metabolic factors may also be required by other parasites of the phylum Apicomplexa, constituting shared unifying fingerprints across different species. If successful, our results would broaden existing knowledge on host-pathogen interactions and open new possibilities to develop therapeutic approaches to treat toxoplasmosis by specifically targeting the host instead of the parasite.