The Melaminophenyl Arsenicals Melarsoprol and Melarsen Oxide Interfere with Thiamine Metabolism in the Fission Yeast Schizosaccharomyces pombe
- Schweingruber, M. Ernst Institute of Cell Biology, University of Bern, Bern, Switzerland
Published in:
- Antimicrobial Agents and Chemotherapy. - American Society for Microbiology. - 2004, vol. 48, no. 9, p. 3268-3271
English
ABSTRACT
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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1128/aac.48.9.3268-3271.2004
- ISSN 0066-4804
- Persistent URL
- https://sonar.ch/global/documents/9629
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