In Vitro Generation of Human High-Density-Lipoprotein-ResistantTrypanosoma brucei brucei Academic Article uri icon

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abstract

  • The host range of African trypanosomes is influenced by innate protective molecules in the blood of primates. A subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I, apolipoprotein L-I, and haptoglobin-related protein is toxic toTrypanosoma brucei bruceibut not the human sleeping sickness parasiteTrypanosoma brucei rhodesiense. It is thought thatT. b. rhodesienseevolved from aT. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypanosomal activity of human HDL. To directly investigate this possibility, we developed an in vitro selection to generate human HDL-resistantT. b. brucei. Here we show that conversion ofT. b. bruceifrom human HDL sensitive to resistant correlates with changes in the expression of the variant surface glycoprotein (VSG) and abolished uptake of the cytotoxic human HDLs. Complete transcriptome analysis of the HDL-susceptible and -resistant trypanosomes confirmed that VSG switching had occurred but failed to reveal the expression of other genes specifically associated with human HDL resistance, including the serum resistance-associated gene (SRA) ofT. b. rhodesiense. In addition, we found that while the original active expression site was still utilized, expression of three expression site-associated genes (ESAG) was altered in the HDL-resistant trypanosomes. These findings demonstrate that resistance to human HDLs can be acquired byT. b. brucei.

authors

  • Faulkner, Sara D
  • Oli, Monika W
  • Kieft, Rudo
  • Cotlin, Laura
  • Widener, Justin
  • Shiflett, April
  • Cipriano, Michael J
  • Pacocha, Sarah E
  • Birkeland, Shanda R
  • Hajduk, Stephen L
  • McArthur, Andrew

publication date

  • August 2006