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Antimicrobial Agents and Chemotherapy, September 2004, p. 3268-3271, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3268-3271.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Melaminophenyl Arsenicals Melarsoprol and Melarsen Oxide Interfere with Thiamine Metabolism in the Fission Yeast Schizosaccharomyces pombe

M. Ernst Schweingruber*

Institute of Cell Biology, University of Bern, Bern, Switzerland

Received 10 March 2004/ Returned for modification 23 March 2004/ Accepted 26 April 2004

The melaminophenyl arsenical melarsoprol is the main drug used against late-stage sleeping sickness caused by Trypanosoma brucei subspecies. Its active metabolite in the human body is melarsen oxide. Here, it is shown that this metabolite inhibits growth of the fission yeast Schizosaccharomyces pombe and that its toxicity can be abolished efficiently by thiamine (vitamin B1), thiamine analogues, and the pyrimidine moiety of the thiamine molecule. Uptake of melarsen oxide is mediated by a membrane protein (car1p), which is involved in the uptake of thiamine and its pyrimidine moiety. Melarsoprol is taken up by cells in a thiamine- and car1p-dependent manner but is not toxic to cells.

* Mailing address: Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland. Phone: 041 31 6314658. Fax: 041 31 6314684. E-mail: sgruber{at}izb.unibe.ch.

Antimicrobial Agents and Chemotherapy, September 2004, p. 3268-3271, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3268-3271.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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