Open AccessThe Melaminophenyl Arsenicals Melarsoprol and Melarsen Oxide Interfere with Thiamine Metabolism in the Fission Yeast Schizosaccharomyces pombe
Author(s) -
M. Ernst Schweingruber
Publication year - 2004
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.48.9.3268-3271.2004
Subject(s) - schizosaccharomyces pombe , yeast , schizosaccharomyces , thiamine , biology , metabolism , microbiology and biotechnology , chemistry , biochemistry , saccharomyces cerevisiae
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 B(1)), 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.