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 Paul, K. S.
Right arrow Articles by Englund, P. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paul, K. S.
Right arrow Articles by Englund, P. T.

 Previous Article  |  Next Article 

Eukaryotic Cell, August 2004, p. 855-861, Vol. 3, No. 4
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.4.855-861.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Multiple Triclosan Targets in Trypanosoma brucei

Kimberly S. Paul,1 Cyrus J. Bacchi,2 and Paul T. Englund1*

Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,1 Haskins Laboratories and Biology Department, Pace University, New York, New York 100432

Received 31 March 2004/ Accepted 30 April 2004

Trypanosoma brucei genes encoding putative fatty acid synthesis enzymes are homologous to those encoding type II enzymes found in bacteria and organelles such as chloroplasts and mitochondria. It was therefore not surprising that triclosan, an inhibitor of type II enoyl-acyl carrier protein (enoyl-ACP) reductase, killed both procyclic forms and bloodstream forms of T. brucei in culture with 50% effective concentrations (EC50s) of 10 and 13 µM, respectively. Triclosan also inhibited cell-free fatty acid synthesis, though much higher concentrations were required (EC50s of 100 to 200 µM). Unexpectedly, 100 µM triclosan did not affect the elongation of [3H]laurate (C12:0) to myristate (C14:0) in cultured bloodstream form parasites, suggesting that triclosan killing of trypanosomes may not be through specific inhibition of enoyl-ACP reductase but through some other mechanism. Interestingly, 100 µM triclosan did reduce the level of incorporation of [3H]myristate into glycosyl phosphatidylinositol species (GPIs). Furthermore, we found that triclosan inhibited fatty acid remodeling in a cell-free assay in the same concentration range required for killing T. brucei in culture. In addition, we found that a similar concentration of triclosan also inhibited the myristate exchange pathway, which resides in a distinct subcellular compartment. However, GPI myristoylation and myristate exchange are specific to the bloodstream form parasite, yet triclosan kills both the bloodstream and procyclic forms. Therefore, triclosan killing may be due to a nonspecific perturbation of subcellular membrane structure leading to dysfunction in sensitive membrane-resident biochemical pathways.

* Corresponding author. Mailing address: Dept. of Biological Chemistry, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3790. Fax: (410) 955-7810. E-mail: penglund{at}jhmi.edu.

Eukaryotic Cell, August 2004, p. 855-861, Vol. 3, No. 4
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.4.855-861.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dayan, F. E., Ferreira, D., Wang, Y.-H., Khan, I. A., McInroy, J. A., Pan, Z. (2008). A Pathogenic Fungi Diphenyl Ether Phytotoxin Targets Plant Enoyl (Acyl Carrier Protein) Reductase. Plant Physiol. 147: 1062-1071 [Abstract] [Full Text]  
  • Stephens, J. L., Lee, S. H., Paul, K. S., Englund, P. T. (2007). Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei. J. Biol. Chem. 282: 4427-4436 [Abstract] [Full Text]  
  • Mazumdar, J., H. Wilson, E., Masek, K., A. Hunter, C., Striepen, B. (2006). Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proc. Natl. Acad. Sci. USA 103: 13192-13197 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»