Abstract

The thioredoxin reductase gene TRR1 has been reported to be overexpressed whenCandida albicans is exposed to oxidative stress. To elucidate the role of TRR1 in the response to oxidative stress and in the pathogenicity of C. albicans, we attempted to disrupt both alleles of this gene using gene-disruption cassettes containing LEU2 andHIS1 as selection markers. The disruption cassettes were transformed into C. albicansSN87 (leu2, his1) to knockout both TRR1 alleles. Despite the successful creation of heterozygous TRR1 mutants, several attempts to create homozygous mutants were unsuccessful, indicating that this gene is required for survival. Exposure to different concentrations of hydrogen peroxide indicated that the heterozygotic mutants, NZ1 (TRR1/trr1, LEU2/leu2) and NZ2 (TRR1/trr1, HIS1/his1), were more sensitive to oxidative stress, compared with wild-type. Virulence studies carried out in mice revealed that the average survival time of mice infected with wild-type C. albicans was 4 days, whereas the average survival time of mice infected with the NZ1 and NZ2 mutants was 17.2 and 16.8 days, respectively. These results indicate that TRR1 is crucial for C. albicans survival and pathogenicity.

Key word: Candida albicans, oxidative stress, thioredoxin reductase, gene disruption and pathogenicity