A Hyperactive Form of the Zinc Cluster Transcription Factor Stb5 Causes Overexpression and Beauvericin Resistance in Candida albicans.

Gain-of-function mutations in the zinc cluster transcription factors Mrr1, Tac1, and Upc2, which result in constitutive overexpression of their target genes, are a frequent cause of fluconazole resistance in the pathogenic yeast In this study, we show that an activated form of another zinc cluster transcription factor, Stb5, confers resistance to the natural compound beauvericin via the overexpression of , encoding an efflux pump of the ATP-binding cassette transporter superfamily. Beauvericin was recently shown to potentiate the activity of azole drugs against Although Yor1 did not contribute to fluconazole resistance when cells were treated with the drug alone, Stb5-mediated overexpression diminished the synergistic effect of the fluconazole-beauvericin combination, thereby enhancing fluconazole resistance in beauvericin-treated cells. Stb5-mediated overexpression also suppressed the inhibition of hyphal growth, an important virulence trait of , by beauvericin. Therefore, activating mutations in Stb5, which result in constitutive overexpression, may enable to acquire resistance to beauvericin and thereby overcome both the sensitization to azole drugs and the inhibition of morphogenesis caused by this compound.