Abstract: Candida spp. are common and aggressive pathogens. Because of the growing resistance of Candida spp. to current antifungals, novel targets, found in Candida spp. but not in humans or other flora, have to be identified. The alternative oxidase (AOX) is one such possibility. This enzyme is insensitive to cyanide, but is sensitive to compounds such as salicylhydroxamic acid (SHAM), disulfiram and n-alkyl gallates. The growth each of six Candida spp. was inhibited significantly by ~13 mM SHAM or 2 mM cyanide, albeit to differing extents. In C. dubliniensis, C. krusei and C. tropicalis the rate of O2 uptake was inhibited by 18-36% by 25 mM SHAM, but this had little or no effect on C. glabrata, C. guilliermondii or C. parapsilosis. Although SHAM substantially inhibited the growth of Candida spp., it is unlikely that the inhibition of AOX was the cause. Salicylhydroxamic acid is used therapeutically in the treatment of urinary tract infections and urolithiasis, but it also has some potential in the treatment of Candida spp. infection.
Abstract: Candida spp. are common and aggressive pathogens.
Because of the growing resistance of Candida spp. to current
antifungals, novel targets, found in Candida spp. but not in humans
or other flora, have to be identified. The alternative oxidase (AOX)
is one such possibility. This enzyme is insensitive to cyanide, but is
sensitive to compounds such as salicylhydroxamic acid (SHAM),
disulfiram and n-alkyl gallates. The growth Candida albicans was
inhibited by SHAM (Ki = 9-15 mM) and cyanide (Ki = 2-4 mM),
albeit to differing extents. The rate of O2 uptake was inhibited by
less than 10% by 25 mM SHAM and by about 90% by 250 μM
KCN. Although SHAM substantially inhibited the growth of C.
albicans, it is unlikely that the inhibition of AOX was the cause.
Salicylhydroxamic acid is used therapeutically in the treatment of
urinary tract infections and urolithiasis, but it also has some potential
in the treatment of C. albicans infection.
Abstract: Candida albicans ATCC 10231 had low endogenous activity of the alternative oxidase compared with that of C. albicans ATCC 10261. In C. albicans ATCC 10231 the endogenous activity declined as the cultures aged. Alternative oxidase activity could be induced in C. albicans ATCC 10231 by treatment with cyanide, but the induction of this activity required the presence of oxygen which could be replaced, at least in part, with high concentrations of potassium ferricyanide. We infer from this that the expression of the gene encoding the alternative oxidase is under the control of a redoxsensitive transcription factor.