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Candida auris vacuolar calcium pump mediates fluconazole efflux and resistance evolution - PubMed

5 days ago
  • #Candida auris
  • #CDT1
  • #fluconazole resistance
  • Candida auris is an emerging fungal pathogen with high intrinsic resistance to fluconazole.
  • A pooled screen of piggyBac transposition mutants identified mitochondrial genes linked to reduced fluconazole susceptibility.
  • The vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) was found responsible for reduced fluconazole susceptibility.
  • Fluconazole induces upregulation of CDT1 via the calcineurin signalling pathway.
  • Cdt1 mediates fluconazole efflux through its plasma membrane localization, dependent on calcineurin and ATP hydrolysis.
  • Cdt1 accelerates the evolution of fluconazole resistance or tolerance and is elevated in resistant clinical isolates.
  • The study reveals a neofunctionalized role for Cdt1 in fluconazole efflux in Candida auris.