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 Coombs, G. H.
Right arrow Articles by Mottram, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coombs, G. H.
Right arrow Articles by Mottram, J. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2001, p. 1743-1745, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1743-1745.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Trifluoromethionine, a Prodrug Designed against Methionine gamma -Lyase-Containing Pathogens, Has Efficacy In Vitro and In Vivo against Trichomonas vaginalis

Graham H. Coombs1,* and Jeremy C. Mottram2

Division of Infection & Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ,1 and Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow G11 6NU,2 United Kingdom

Received 26 January 2001/Returned for modification 5 March 2001/Accepted 21 March 2001

Methionine gamma -lyase, the enzyme which catalyzes the single-step conversion of methionine to alpha -ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasite Trichomonas vaginalis, to anaerobic bacteria containing methionine gamma -lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.

* Corresponding author. Mailing address: Division of Infection & Immunity, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, United Kingdom. Phone: 44 141 330 4777. Fax: 44 141 330 3516. E-mail: g.coombs{at}bio.gla.ac.uk.

Antimicrobial Agents and Chemotherapy, June 2001, p. 1743-1745, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1743-1745.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ali, V., Nozaki, T. (2007). Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by "Amitochondriate" Protozoan Parasites. Clin. Microbiol. Rev. 20: 164-187 [Abstract] [Full Text]  
  • Westrop, G. D., Goodall, G., Mottram, J. C., Coombs, G. H. (2006). Cysteine Biosynthesis in Trichomonas vaginalis Involves Cysteine Synthase Utilizing O-Phosphoserine. J. Biol. Chem. 281: 25062-25075 [Abstract] [Full Text]  
  • Kleydman, Y., Yarlett, N., Gorrell, T. E. (2004). Production of ammonia by Tritrichomonas foetus and Trichomonas vaginalis. Microbiology 150: 1139-1145 [Abstract] [Full Text]  
  • Rooseboom, M., Commandeur, J. N. M., Vermeulen, N. P. E. (2004). Enzyme-Catalyzed Activation of Anticancer Prodrugs. Pharmacol. Rev. 56: 53-102 [Abstract] [Full Text]  
  • Tokoro, M., Asai, T., Kobayashi, S., Takeuchi, T., Nozaki, T. (2003). Identification and Characterization of Two Isoenzymes of Methionine {gamma}-Lyase from Entamoeba histolytica: A KEY ENZYME OF SULFUR-AMINO ACID DEGRADATION IN AN ANAEROBIC PARASITIC PROTIST THAT LACKS FORWARD AND REVERSE TRANS-SULFURATION PATHWAYS. J. Biol. Chem. 278: 42717-42727 [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»