Characterization of thiamine uptake and utilization in Candida spp. subjected to oxidative stress.

Abstract

Candida species are associated with an increasing number of life-threatening infections (candidiases), mainly due to the high resistance of these yeast-like fungi to antifungal drugs and oxidative stress. Recently, thiamine (vitamin B1) was found to alleviate stress responses in Saccharomyces cerevisiae; however, thiamine influence on defense systems in pathogenic fungi has never been investigated. The current work was aimed to elucidate the role of thiamine in stress reactions of C. albicans, C. glabrata, C. tropicalis and C. dubliniensis, subjected to hydrogen peroxide treatment. As compared to S. cerevisiae, Candida strains exposed to oxidative stress showed: (i) a much higher dependence on exogenous thiamine; (ii) an increased demand for thiamine diphosphate (TDP) and TDP-dependent enzyme, transketolase; (iii) no changes in gene expression of selected stress markers - superoxide dismutase and catalase - depending on thiamine availability in medium; (iv) a similar decrease of reactive oxygen species (ROS) generation in the presence of thiamine. Moreover, the addition of therapeutic doses of thiamine to yeast culture medium revealed differences in its accumulation between various Candida species. The current findings implicate that the protective action of thiamine observed in S. cerevisiae differs significantly form that in pathogenic Candida strains, both in terms of the cofactor functions of TDP and the effects on fungal defense systems.