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Eukaryotic Cell, August 2006, p. 1276-1286, Vol. 5, No. 8
1535-9778/06/$08.00+0     doi:10.1128/EC.00116-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei

Sara D. Faulkner,1 Monika W. Oli,2 Rudo Kieft,1 Laura Cotlin,1,3 Justin Widener,1 April Shiflett,1 Michael J. Cipriano,1 Sarah E. Pacocha,4 Shanda R. Birkeland,1 Stephen L. Hajduk,1* and Andrew G. McArthur1

Josephine Bay Paul Center, Global Infectious Disease Program, Marine Biological Laboratory, 7 MBL Street, Woods Hole, Massachusetts 02543,1 Banyan Biomarkers, Alachua, Florida 32615,2 Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294,3 Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 025434

Received 19 April 2006/ Accepted 13 June 2006

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 to Trypanosoma brucei brucei but not the human sleeping sickness parasite Trypanosoma brucei rhodesiense. It is thought that T. b. rhodesiense evolved from a T. 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-resistant T. b. brucei. Here we show that conversion of T. b. brucei from 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) of T. 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 by T. b. brucei.

* Corresponding author. Mailing address: Josephine Bay Paul Center, Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543. Phone: (508) 289-3171. Fax: (508) 457-4727. E-mail: shajduk{at}mbl.edu.

Eukaryotic Cell, August 2006, p. 1276-1286, Vol. 5, No. 8
1535-9778/06/$08.00+0     doi:10.1128/EC.00116-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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