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: Fungal infections are becoming more common and the
range of susceptible individuals has expanded. While Candida
albicans remains the most common infective species, other Candida
spp. are becoming increasingly significant. In a range of large-scale
studies of candidaemia between 1999 and 2006, about 52% of 9717
cases involved C. albicans, about 30% involved either C. glabrata or
C. parapsilosis and less than 15% involved C. tropicalis, C. krusei or
C. guilliermondii. However, the probability of mortality within 30
days of infection with a particular species was at least 40% for C.
tropicalis, C. albicans, C. glabrata and C. krusei and only 22% for
C. parapsilopsis. Clinical isolates of Candida spp. grew at rates
ranging from 1.65 h-1 to 4.9 h-1. Three species (C. krusei, C. albicans
and C. glabrata) had relatively high growth rates (μm > 4 h-1), C.
tropicalis and C. dubliniensis grew moderately quickly (Ôëê 3 h-1) and
C. parapsilosis and C. guilliermondii grew slowly (< 2 h-1). Based
on these data, the log of the odds of mortality within 30 days of
diagnosis was linearly related to μm. From this the underlying
probability of mortality is 0.13 (95% CI: 0.10-0.17) and it increases
by about 0.09 ± 0.02 for each unit increase in μm. Given that the
overall crude mortality is about 0.36, the growth of Candida spp.
approximately doubles the rate, consistent with the results of larger
case-matched studies of candidaemia.