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<p><i>Candida auris</i> is an emerging multidrug-resistant yeast pathogen that poses a serious global health threat. In particular, fluconazole resistance is common in <i>C. auris</i>, posing challenges for treating invasive infections. Understanding the genetic and molecular mechanisms underlying fluconazole resistance in <i>C. auris</i> is crucial for developing effective control strategies. The current study investigated the genetic and molecular basis of fluconazole resistance in <i>C. auris</i> clade V isolates. Furthermore, we examined mutations in ergosterol biosynthesis genes and expression of efflux pump genes in fluconazole-resistant versus susceptible in strains Clade V. Two <i>C. auris</i> isolates, one fluconazole-resistant, and one fluconazole-susceptible, were subjected to qPCR analysis of efflux pump gene (<i>CDR1, CDR2, MDR1, MDR2</i>) expression. Protein structure modeling was also performed to assess the impact of mutation in the ergosterol biosynthesis gene (<i>ERG11</i>) on antifungal drug accessibility. qPCR analysis revealed no significant difference in the expression levels of the efflux pump genes <i>CDR1</i>, <i>CDR2</i>, and <i>MDR1</i> between the resistant and susceptible strains. Protein structure modeling indicated that the Y132F mutation in <i>ERG11</i> likely altered fluconazole binding and accessibility. This study provides insights into the genetic and molecular mechanisms underpinning fluconazole resistance in <i>C. auris</i> Clade V. The findings highlight the critical roles of <i>ERG11</i> mutation in mediating azole resistance in this emerging fungal pathogen.</p>

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Deciphering Fluconazole Resistance in Candida auris clade V: The Role of Efflux Pump Gene Expression and Ergosterol Pathway Mutations

  • 期刊论文

  • 发表日期：

    2025年4月17日

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  • Robab Ebrahimi Barough,
  • Mahdi Abastabar,
  • Maryam Moazeni,
  • Javad Javidnia,
  • Reza Valadan,
  • Azadeh Bandegani,
  • Mohsen Nosratabadi,
  • Iman Haghani,
  • Bram Spruijtenburg,
  • Darius Armstrong-James,
  • Hamid Badali

摘要

Candida auris is an emerging multidrug-resistant yeast pathogen that poses a serious global health threat. In particular, fluconazole resistance is common in C. auris, posing challenges for treating invasive infections. Understanding the genetic and molecular mechanisms underlying fluconazole resistance in C. auris is crucial for developing effective control strategies. The current study investigated the genetic and molecular basis of fluconazole resistance in C. auris clade V isolates. Furthermore, we examined mutations in ergosterol biosynthesis genes and expression of efflux pump genes in fluconazole-resistant versus susceptible in strains Clade V. Two C. auris isolates, one fluconazole-resistant, and one fluconazole-susceptible, were subjected to qPCR analysis of efflux pump gene (CDR1, CDR2, MDR1, MDR2) expression. Protein structure modeling was also performed to assess the impact of mutation in the ergosterol biosynthesis gene (ERG11) on antifungal drug accessibility. qPCR analysis revealed no significant difference in the expression levels of the efflux pump genes CDR1, CDR2, and MDR1 between the resistant and susceptible strains. Protein structure modeling indicated that the Y132F mutation in ERG11 likely altered fluconazole binding and accessibility. This study provides insights into the genetic and molecular mechanisms underpinning fluconazole resistance in C. auris Clade V. The findings highlight the critical roles of ERG11 mutation in mediating azole resistance in this emerging fungal pathogen.