Discussion

T. brucei relies on uptake of host fatty acids and de novo synthesis to meet its fatty acid needs. We hypothesized T. brucei modulates Acetyl-CoA Carboxylase (TbACC), the first step in fatty acid synthesis, in response to environmental lipids. To test our hypothesis, bloodstream (BF) and procyclic forms (PF) were grown in low, normal, or high lipid media (prepared by modulating media serum) and the effect on TbACC mRNA, protein, and enzymatic activity was examined. qRT-PCR analysis of TbACC mRNA levels showed no significant difference, indicating little transcriptional regulation in response to environmental lipids. In BFs, media lipids had no effect on TbACC protein levels or activity, but in PFs we observed 2.7-fold lower TbACC protein levels and 37% lower TbACC activity in high lipid compared to low lipid media. Supplementation of low lipid media with fatty acids mimicked the effect of high lipids on TbACC activity, suggesting this effect was due to the lipid component of the media. In PFs TbACC phosphorylation increased by 3.9-fold in high lipid compared to low lipid media, and phosphorylation was shown to inactivate TbACC. These results demonstrated that PFs possess an environmental response pathway that enables PFs to monitor the host lipid supply and modulate TbACC and fatty acid synthesis accordingly.