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.

Riboflavin Targets the Cellular Metabolic and Ribosomal Pathways of Candida albicans In Vitro and Exhibits Efficacy against Oropharyngeal Candidiasis

“…The production of ROS may connect total metabolism via thiamine metabolism, RF metabolism, and ribosome metabolism caused by exogenous RF ( Fig. 8 ) ( 48 – 51 ). More specifically, exogenous RF targets the thiamine and RF metabolic pathways, thus disrupting central carbon metabolism.…”

“…This further aggravates the disorder in thiamine metabolism, since histidine is the substrate for thiamine synthesis. Moreover, ROS are capable of inducing protein damage and interacting with endogenous RF and thiamine metabolism ( 35 , 48 – 51 ). The accumulating pyruvate may defend against ROS ( 36 ).…”

NIH4215: A mutation-prone thiamine auxotrophic clinical Aspergillus fumigatus isolate

“…In addition, we observed that strain NIH4215 seems to have an efficient thiamine uptake system since less than 1 µg/ml of thiamine still supported growth albeit the growth rate was slightly reduced when compared to high thiamine supplementation levels. Increased thiamine concentrations have been shown to cause a beneficial effect on stress tolerance in yeasts ( Wolak et al., 2014 ; Wolak et al., 2015 ) and the same may apply to A. fumigatus . Both thiamine prototrophic A. fumigatus wild-type strains, Af293 and CBS144.89, showed increased germination and growth rate in the presence of elevated thiamine concentrations.…”

Protective effects of thiamine on Wickerhamomyces anomalus against ethanol stress

“…In addition, thiamine was reported had protective effects in Candida spp. against oxidative stress ( Wolak et al, 2015 ). Here, we found that thiamine alleviated the inhibitory effect of ethanol stress on the W. anomalus cells probably by improving energy metabolism ( Figures 5 , 6 ), and the underlying mechanism of thiamine mediation will be further explored in the future.…”