Eukaryotic Cell
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oli, M. W.
Right arrow Articles by Hajduk, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oli, M. W.
Right arrow Articles by Hajduk, S. L.

 Previous Article  |  Next Article 

Eukaryotic Cell, January 2006, p. 132-139, Vol. 5, No. 1
1535-9778/06/$08.00+0     doi:10.1128/EC.5.1.132-139.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Serum Resistance-Associated Protein Blocks Lysosomal Targeting of Trypanosome Lytic Factor in Trypanosoma brucei

Monika W. Oli,3,{dagger},{ddagger} Laura F. Cotlin,1,2,{ddagger} April M. Shiflett,1 and Stephen L. Hajduk1*

Global Infectious Disease Program, Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, Massachusetts 20543,1 Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35292,2 Departments of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 352923

Received 26 August 2005/ Accepted 6 October 2005

Trypanosoma brucei brucei is the causative agent of nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. A minor subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I (apoA-I), apolipoprotein L-I (apoL-I), and haptoglobin-related protein (Hpr) provides this innate protection against T. b. brucei infection. This HDL subfraction, called trypanosome lytic factor (TLF), kills T. b. brucei following receptor binding, endocytosis, and lysosomal localization. Trypanosoma brucei rhodesiense, which is morphologically and physiologically indistinguishable from T. b. brucei, is resistant to TLF-mediated killing and causes human African sleeping sickness. Human infectivity by T. b. rhodesiense correlates with the evolution of a resistance-associated protein (SRA) that is able to ablate TLF killing. To examine the mechanism of TLF resistance, we transfected T. b. brucei with an epitope-tagged SRA gene. Transfected T. b. brucei expressed SRA mRNA at levels comparable to those in T. b. rhodesiense and was highly resistant to TLF. In the SRA-transfected cells, intracellular trafficking of TLF was altered, with TLF being mainly localized to a subset of SRA-containing cytoplasmic vesicles but not to the lysosome. These results indicate that the cellular distribution of TLF is influenced by SRA expression and may directly determine the organism's susceptibility to TLF.

* Corresponding author. Mailing address: Josephine Bay Paul Center, Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543. Phone: (508) 289-7131. Fax: (508) 457-4727. E-mail: shajduk{at}mbl.edu.

{dagger} Present address: Banyan Biomarkers, Alachua, FL 32615.

{ddagger} M.W.O. and L.F.C. contributed equally to this work.

Eukaryotic Cell, January 2006, p. 132-139, Vol. 5, No. 1
1535-9778/06/$08.00+0     doi:10.1128/EC.5.1.132-139.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Appl. Environ. Microbiol. Infect. Immun. J. Bacteriol.
Mol. Cell Biol. Microbiol. Mol. Biol. Rev. ALL ASM JOURNALS
Copyright © 2006 by the American Society for Microbiology.