Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans

Antimicrob Agents Chemother. 2015 Nov 23;60(2):1145-7. doi: 10.1128/AAC.02043-15. Print 2016 Feb.

Abstract

Hospitalized ill patients, at risk for invasive candidiasis, often receive multiple medications, including proton pump inhibitors (PPIs). The antifungal fluconazole perturbs the vacuolar proton ATPase. The PPI omeprazole antagonized Candida albicans growth inhibition by fluconazole. A C. albicans codon-adapted pHluorin, Ca.pHluorin, was generated to measure cytosolic pH. The fungal cytosol was acidified by omeprazole and realkalinized by coexposure to fluconazole. Vacuolar pH was alkalinized by fluconazole. Off-target effects of any medication on fungal pathogens may occur.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Cytosol / drug effects
  • Drug Antagonism
  • Fluconazole / antagonists & inhibitors*
  • Fluconazole / pharmacology
  • Hydrogen-Ion Concentration
  • Omeprazole / pharmacology*
  • Proton Pump Inhibitors / pharmacology*

Substances

  • Antifungal Agents
  • Proton Pump Inhibitors
  • Fluconazole
  • Omeprazole