Living high on the hog or down in the dumps: How fatty acid synthesis helps African trypanosomes survive in host environments.

Authors:

Sunayan S Ray, Ciara Anderson Mcknight, Kimberly Paul

PI/Advisor:

Dr Kimberly Paul

Program:

Biochemistry and Molecular Biology (College of Agriculture, Forestry and Life Sciences)

Abstract:

Trypanosoma brucei is a major cause of death in humans (sleeping sickness) and livestock in some parts of Africa. It is caused by a parasite Trypanosoma brucei, which is transmitted by the Tsetse fly. Current drugs are toxic and vaccine development is unlikely because the parasites undergo antigenic variation. Antigenic variation involves the switching of Variant Surface Glycoproteins (VSGs), which depends on fatty acids for surface expression. Acetyl-CoA Carboxylase (ACC) catalyzes the first committed step of fatty acid synthesis and hence is a potential therapeutic target. Our studies demonstrated that inhibition of ACC expression causes a growth defect in insect procyclic form (PF) parasites in low lipid condition and reduced mammalian bloodstream form (BF) infection in mice. Under lab growth conditions, we observed regulation of ACC by environmental lipids in PFs but not BFs. In BFs, we showed that ACC is required for the elevated endocytosis needed for the parasite to avoid antibody-dependent complement-mediated lysis. In sum, we propose that in PFs, ACC is regulated to maintain lipid levels while the parasite undergoes development in the Tsetse fly, while in BFs, ACC is always active to support the upregulation of endocytosis needed to evade the mammalian immune system.

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