Expression of Candida glabrata adhesins after exposure to chemical preservatives

Adherence of Candida glabrata, an opportunistic yeast pathogen, to host cells is mediated in part by the Epa family of adhesins, which are encoded largely at subtelomeric loci, where they are subject to transcriptional silencing. In analyzing the regulation of the subtelomeric EPA6 gene, we found that its transcription is highly induced after exposure to methylparaben, propylparaben, or sorbate. These weak acid-related chemicals are widely used as antifungal preservatives in many consumer goods, including over-the-counter vaginal products. Culture of C. glabrata with a variety of vaginal products induced expression of EPA6, leading to increased adherence to cultured human cells as well as primary human vaginal epithelial cells. We present evidence that paraben/sorbate induction of EPA6 expression involves both preservative stress and growth under hypoxic conditions. We further show that activation of EPA6 transcription depends on the Flo8 and Mss11 transcription factors and does not require the classic weak-acid transcription factors War1 or Msn2/Msn4. We conclude that exposure of C. glabrata to commonly used preservatives can alter the expression of virulence-related genes.