Influence of boric acid on energy metabolism and stress tolerance of Candida albicans

Abstract

Boron presents at physiological pH in the form of boric acid (BA), a molecule that has both positive and negative effects on biological processes. In medicine, BA is used as a topical treatment for vaginal yeast infections by Candida species because of its well-documented but poorly understood effect on inhibition of growth in general and of invasive, hyphal growth in particular. The present study examines the influence of BA on carbohydrate energy metabolism of this common human pathogen. Starting from previous findings about an inhibition of key NAD-dependent enzymes by BA in vitro, we confirmed that such an inhibition occurs in permeabilized C. albicans cells. Cultures growing even with moderate concentrations of BA experience mitochondrial failure, increase ethanol production from glucose and decrease the deposition of carbohydrate stores in the form of glycogen. Cells growing on the non-fermentable, FAD-generating carbon source lactate have a higher BA tolerance, which suggests that the toxicity of BA is rooted in an inhibition of NAD-dependent reactions and the increased production of ethanol. Boric acid exposure sensitizes C. albicans selectively to the toxic effects of ethanol. This additive effect suggests that the endogenously produced ethanol increases the load on ethanol resistance mechanisms. Lastly, combination studies showed no interactions of BA with common antifungal drugs, meaning that addition of BA to topical formulations can provide an additive antifungal effect regardless of the chosen active ingredient.