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- W1523163054 abstract "Trypanosoma brucei, a protozoan parasite transmitted by the tsetse fly, invades the bloodstream and CNS of humans, causing African sleeping sickness. In addition to antigenic variation of its surface glycoprotein coat, T. brucei employs a second immune evasion tactic: upregulation of endocytosis to clear lytic cell surface immune complexes, a strategy likely involving membrane turnover and fatty acid synthesis (FAS). Acetyl-CoA carboxylase (ACC) catalyzes the first committed step of FAS and is a regulatory control point. Previous work showed that ACC RNA interference (RNAi) in T. brucei bloodstream forms (BFs) reduced virulence in mice, but had no effect on growth in culture. We hypothesized that ACC is required in BFs for immune evasion via endocytosis upregulation. We examined endocytosis in BF ACC RNAi cells and observed a 90% reduction in fluid phase and receptor-mediated endocytosis upon ACC RNAi. ACC RNAi also caused a 30% delay in the clearance of surface-bound antibodies and 40% increase in the susceptibility to complement-mediated lysis. Because endocytosis upregulation may increase demand for FAS, we examined if ACC is regulated in response to changes in lipid supply. In BFs, we found no change in ACC expression, activity, or phosphorylation upon growth in low or high lipid media. Also, ACC RNAi had similar effects on endocytosis, antibody clearance, and complement-mediated lysis under low and high lipid conditions. In contrast, insect form cells exhibited a 2X increase in ACC protein and enzymatic activity in low lipid media. Phosphorylation of insect form ACC increased 3X in high lipid media and decreased by 80% in low lipid media. We propose a model whereby T. brucei ACC is up-regulated in the mammalian host to support increased endocytosis and immune evasion, while in the insect host, ACC is regulated in response to the environmental lipid supply. Grant Funding Source: Supported by NIH R15 AI081207" @default.
- W1523163054 created "2016-06-24" @default.
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- W1523163054 date "2014-04-01" @default.
- W1523163054 modified "2023-09-26" @default.
- W1523163054 title "The host is a harsh mistress: role of fatty acid synthesis in trypanosome survival (1001.6)" @default.
- W1523163054 doi "https://doi.org/10.1096/fasebj.28.1_supplement.1001.6" @default.
- W1523163054 hasPublicationYear "2014" @default.
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