TgATAT-Mediated α-Tubulin Acetylation Is Required for Division of the Protozoan Parasite Toxoplasma gondii

What is it about?

Toxoplasma gondii is an opportunistic parasite of immunocompromised patients that is transmitted by cats or contaminated food/water. New drugs to stop the parasite from replicating in the body are urgently needed. In this study, we identified new factors that are involved in the replication of this parasite. The factors play a role in stabilizing a critical part of the parasite's cytoskeleton called microtubules.

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Why is it important?

Toxoplasma gondii is an opportunistic parasite that infects at least one-third of the world population. New treatments for the disease (toxoplasmosis) are needed since current drugs are toxic to patients. Microtubules are essential cellular structures built from tubulin that show promise as antimicrobial drug targets. Microtubules can be regulated by chemical modification, such as acetylation on lysine-40 (K40). To determine the role of K40 acetylation in Toxoplasma, and whether it is a liability to the parasite, we performed mutational analyses of the α-tubulin gene. Our results indicate that parasites cannot survive without K40 acetylation unless microtubules are stabilized with a secondary mutation. Additionally, we identified the parasite enzyme that acetylates α-tubulin (TgATAT). Genetic disruption of TgATAT caused severe defects in parasite replication, further highlighting the importance of α-tubulin K40 acetylation in Toxoplasma and its promise as a potential new drug target.