Protein fatty acylation and Toxoplasma gondii dissemination

CORVI, MM

Congreso; New Insights into Lipidation in Cell Biology; 2021

British Biochemical Society

Toxoplasmagondii, the causative agent of toxoplasmosis, is anopportunistic pathogen that affects one third of the global population.Toxoplasmosis in humans is asymptomatic but is capable of causing devastatingdisease in immunocompromised individuals and the developing fetus. Being an obligateintracellular pathogen, host-cell invasion is a vital process, highlycoordinated and dependent on its unique gliding machinery (glideosome). The glideosomeis localized to the parasite pellicle, between the plasma membrane and theinner membrane complex and allows T. gondii dissemination by powering itsmotility and host-cell invasion. I will present our advances in understandingthe impact of protein palmitoylation and myristoylation in T. gondiidissemination. A special focus will be on the impact of inhibiting proteinpalmitoylation in processes such as host-cell invasion and gliding. Inaddition, many proteins located to the glideosome are palmitoylated, whichsupports the importance of this protein modification in these processes. I willpresent recent data on myristoylation in this parasite as well. T. gondiiencodes for a single N-myristoyl transferase (TgNMT) which is homologous toother parasitic NMTs. This enzyme is expressed along the lytic cycle and itsactivity is necessary for parasite survival. Altogether, the results presented showthat protein fatty acylation is key to T. gondii dissemination and that theseprotein modifications arise as interesting targets of intervention for thetreatment of toxoplasmosis.