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A Hyperactive Form of the Zinc Cluster Transcription Factor Stb5 Causes YOR1 Overexpression and Beauvericin Resistance in Candida albicans.
Ramírez-Zavala, Bernardo; Manz, Hannah; Englert, Frank; Rogers, P David; Morschhäuser, Joachim.
Afiliación
  • Ramírez-Zavala B; Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
  • Manz H; Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
  • Englert F; Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
  • Rogers PD; Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
  • Morschhäuser J; Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany joachim.morschhaeuser@uni-wuerzburg.de.
Article en En | MEDLINE | ID: mdl-30249688
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 Candida albicans 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 YOR1, encoding an efflux pump of the ATP-binding cassette transporter superfamily. Beauvericin was recently shown to potentiate the activity of azole drugs against C. albicans Although Yor1 did not contribute to fluconazole resistance when C. albicans cells were treated with the drug alone, Stb5-mediated YOR1 overexpression diminished the synergistic effect of the fluconazole-beauvericin combination, thereby enhancing fluconazole resistance in beauvericin-treated C. albicans cells. Stb5-mediated YOR1 overexpression also suppressed the inhibition of hyphal growth, an important virulence trait of C. albicans, by beauvericin. Therefore, activating mutations in Stb5, which result in constitutive YOR1 overexpression, may enable C. albicans to acquire resistance to beauvericin and thereby overcome both the sensitization to azole drugs and the inhibition of morphogenesis caused by this compound.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candida albicans / Proteínas Fúngicas / Depsipéptidos Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candida albicans / Proteínas Fúngicas / Depsipéptidos Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos