Thioredoxin reductase is essential for viability in the fungal pathogen Cryptococcus neoformans.
Thioredoxin reductase (TRR1) is an important component of the thioredoxin oxidative stress resistance pathway. Here we show that it is induced during oxidative and nitrosative stress and is preferentially localized to the mitochondria in Cryptococcus neoformans. The C. neoformans TRR1 gene encodes the low-molecular-weight isoform of the thioredoxin reductase enzyme, which shares little homology with that of its mammalian host. By replacing the endogenous TRR1 promoter with an inducible copper transporter promoter, we showed that Trr1 appears to be essential for viability of this pathogenic fungus, making it a potential antifungal target.
Missall
Tricia A
TA
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Lodge
Jennifer K
JK
D002470:Cell Survival; D003455:Cryptococcus neoformans / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D026361:Reactive Nitrogen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D007527:Isoenzymes; D026361:Reactive Nitrogen Species; D011993:Recombinant Fusion Proteins; D013880:Thioredoxin-Disulfide Reductase