Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates.
Enhancement of the anti-oxidant metabolism of Leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. Here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. Elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of peroxides. These data suggest that enhanced anti-oxidant defences may play a significant role in clinical resistance to antimonials.
Wyllie
Susan
S
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH Scotland, UK.
Mandal
Goutam
G
Singh
Neeloo
N
Sundar
Shyam
S
Fairlamb
Alan H
AH
Chatterjee
Mitali
M
D000965:Antimony / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D007893:Leishmania donovani / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000469:parasitology; D010544:Peroxidases / Q000032:analysis*; D010545:Peroxides / Q000378:metabolism; D015800:Protozoan Proteins / Q000032:analysis*; D013879:Thioredoxins / Q000032:analysis
D000981:Antiprotozoal Agents; D010545:Peroxides; D015800:Protozoan Proteins; C114110:tryparedoxin; D013879:Thioredoxins; D000965:Antimony; D010544:Peroxidases; C110959:tryparedoxin peroxidase